Cultural contact between China and Japan has occurred since ancient times. There is a story that is frequently told in the Chinese tradition about the first Emperor (reign: 221-210 B.C.) who is said to have sent emissaries by ship on the Eastern Sea to find the herb of immortality; it is suggested that they returned from Japan with ganoderma (lingzhi; Japanese: reishi Mushroom) in completion of their mission. Some Chinese medical works were introduced to Japan as early as the 4th or 5th Century A.D., coming first by way of Korea, which had adopted Chinese medicine by that time. Historical records indicate that a Korean physician named Te Lai came to Japan in 459 A.D., and that a Chinese Buddhist named Zhi Cong brought medical texts with him to Japan via Korea in 562 A.D. It was also during this period that the Chinese written language was adopted in Japan so that the people could learn from China about Buddhism, Confucianism, governmental organization, and the divination arts, opening the way for study of Chinese medicine.

The first official classes in Chinese medicine in Japan are said to have been given by a Korean physician in 602 A.D. by order of the Empress Seiko (reign: 592-628 A.D.). During her reign, the Japanese court started sending envoys to China. Some of the Japanese visitors to China, being there primarily on diplomatic missions, brought back medical classics of China. In 701, the Taiho Ritsuryo Code (a series of edicts establishing a particular political and academic structure) was compiled and provided for, among many other things, establishment of a ministry of health (Ten'yakuryo; also translated as the Institute of Medicine). This Taiho Code, influenced by two visits to the Tang Imperial Court by the envoy Enichi, included a division devoted to the Chinese concept of yin-yang, one of the foundations of Chinese medical theories and other aspects of Chinese culture. The services of the health ministry were restricted to the royal court and aristocracy, while Buddhist temples took care of the poor, eventually including Chinese medicine. The Empress Kayo (701-760 A.D.) established a dispensary to supply free medicine to the needy in 730 A.D. The dispensary provided local Japanese herbs, but the method of using the herbs was already influenced by Chinese medical principles.

These early contacts and exchanges with Korea and China had only limited implications for medical activities in Japan which, up to that time, had been dominated by shamanism, exorcism, and purifications, with only a slight reliance on herbs, mainly for symbolic use. Widespread interest in Chinese medicine apparently arose as the result of a visit from the Chinese Buddhist priest Juan Zhen (Japanese: Ganjin) who arrived in Japan in 753 A.D. (at the height of the Tang Dynasty in China). Jian Zhen had developed a great knowledge of medicine and herbs. It took five attempts over a period of 12 years before he was able to cross the rough seas to reach Japan. He was blind at the time he arrived, but he was able to accomplish much due to his great generosity. Jian Zhen had come to Japan with medical texts, a collection of herb materials, and a desire to teach. It was said that he had refined his sense of smell so that he could distinguish between true herbs and any false substitutes despite his lack of eyesight. Most importantly, he provided free medical services, which boosted the respect for both Buddhism and Chinese medicine and, along with the charitable act of Empress Kayo a few years earlier, introduced the concept of social medicine to Japan.

A collection of herbs that Jian Zhen and subsequent visitors brought to Japan has been preserved to this day. In the building complex known as the Shosoin (also spelled Seisoyin), resides a collection of herbs that was presented in front of the Buddha statue in the Todaiji Temple at the Imperial Palace (see Figure 1). This collection was dedicated 49 days following the death of the former Emperor Shomu (Seimu Tienno) in 756 A.D. (in the Buddhist system, the determination of rebirth, entry of the spirit into the womb, occurs 49 days after death). The Shosoin has served as a repository and museum for these herbal medicines and miraculously escaped both natural and man-made disasters, making it one of the oldest surviving structures in Japan. The Shosoin had been designed in such a way that it helped prevent the deterioration of the herbs, and it has been ceremoniously aired out for one week each year. According to an inventory record that accompanied the collection, there were 60 different medicinal materials in the original group, though the dispensing of herbs to patients depleted the supplies of 20 of them, leaving 40 of the original samples; there were also 16 herbs that may have been added to the collection after the inventory list was compiled. Scholars have performed analyses of the herb materials to confirm their identity; they have found many of the active ingredients intact after more than 13 centuries.

Following the introduction of Chinese medicine by Jian Zhen, a number of Japanese people took an interest in learning and spreading the tradition in Japan, and they got hold of numerous medical works from China. The Xinxiu Bencao (Newly Revised Materia Medica) also known as the Tang Bencao, Tang Dynasty Materia Medica, 659 A.D.), which had been sponsored by the Tang Imperial Court, became an obligatory text in the study of medicine at the Japanese Health Ministry in 787 A.D. Unfortunately, many of the 844 medicinal substances described in the Materia Medica were not available in Japan at the time.

At the end of the 8th Century, the Japanese physician Ilura Yamanoue traveled to China to study Chinese medicine and wrote a poem, published in a 9th Century anthology, mentioning famous Chinese physicians, such as Bian Que, Hua Tuo, and Zhang Zhongjing. A few medical works by Japanese authors were also written during the 9th Century, such as Datong Leiqi Fang (A Generalization of the Ancient Native Herb Formulas) in 808 A.D. and Jin Lan Fang (Precious Formulas) in 868 A.D. A list of Chinese medical books compiled around 895 A.D. included 166 texts. Around 918 A.D., a Japanese medical dictionary (Honzo-wamyo) was written, quoting from 60 different Chinese medical works.

The growing collection of Chinese works were used as a source of Japan's primary text on Chinese medicine, the Ishimpo (The Essence of Medicine and Therapeutic Methods; Chinese name: Yi Xin Fang). This text of 30 individually titled scrolls was written by Yasuyori Tamba in 984 A.D. and is the oldest Japanese book on the subject to survive to the present. The Ishimpo is a compilation of medical knowledge and medical theories that were prevalent during the Sui Dynasty (589-618 A.D.) and Tang Dynasty (618-907 A.D.), quoting from more than 100 Chinese texts. This period of Chinese medical history was greatly influenced by the work of two earlier medical authorities: Zhang Zhongjing (ca. 150-220 A.D.) and Sun Simiao (581-682 A.D.). Zhang wrote the medical text that was divided into the Shanghan Lun and Jingui Yaolue. Sun Simiao became known in China as the "King of Medicine" or the "Medicine God;" his herb medicine books were the Qianjin Yaofang and Qianjin Yifang (collectively referred to as Qianjin Fang). In turn, Sun Simiao had been influenced, especially with regard to Taoist practices, by the famous alchemist Ge Hong (281-341 A.D.), who published formulas in his book Zhouhou Beiji Fang (ca. 340 A.D.). The Materia Medica guides that were relied upon at the time were the Shennong Bencao Jing (ca. 100 A.D.) in its revised form, Mingyi Bielu by Tao Hongjing (452-536 A.D.), and the Xinxiu Bencao mentioned previously.

Tao Hongjing had classified the herbs of the original Material Medical of China into three groups: upper, middle, and lower herbs. This grouping had a profound impact on the concepts of medical practice during this era. The upper-class herbs were said to be suited for long-term administration to preserve health and attain long life. While there were numerous plant medicines in this category, the dominant ingredient at the time, the one used most often by Taoist seekers of immortality, was cinnabar (mercuric sulfide). Medicines comprised of large amounts of cinnabar, often with realgar, were popularized by Ge Hong and Sun Simiao, who studied the Taoist arts. Of course, these medicines, considered so valuable for regular intake, were actually poisonous, and both Chinese and Japanese seekers of long life suffered the consequences. The middle- and lower-class herbs were to be used for treating specific diseases, used for a relatively short time, and were deemed to be mildly toxic. In fact, they were often less toxic than cinnabar, but a number of very potent drugs were included, such as genkwa and datura, that supported this classification.

The Shanghan Lun and Jingui Yaolue formulas were mostly comprised of plant materials, and the majority had low toxicity. These plant materials were supplemented by minerals or mineralized compounds, most of which were quite safe: oyster shell, dragon bone, gypsum, and talc, for example, are all calcium materials used in some of the formulas. These ancient formulas soon became one of the principal focal points of Kampo medicine. To this day, many Kampo practitioners study and praise the Shanghan Lun and Jingue Yaolue and prescribe their formulas, such as Minor Bupleurum Combination (Xiao Chaihu Tang), Cinnamon and Hoelen Formula (Guizhi Fuling San), Hoelen Five Formula (Wuling San), Pueraria Combination (Gegen Tang), and Tang-kuei and Peony Formula (Danggui Shaoyao San). These are relatively small formulas (typically 5-9 ingredients) that rely heavily on a small collection of herbs, mainly those categorized in modern texts as surface relieving herbs, heat clearing herbs, moisture draining herbs, and tonics.

Japan entered a period of isolation soon after the Ishimpo was published; the last envoy to China returned in 894 A.D. Although there were some individual visits by Japanese scholars to China, the level of exchange was limited. The formulas of Zhang Zhongjing and Sun Simiao, and the accompanying medical theories and practices of their time, dominated Kampo until the end of the 15th Century.