In these ten years, Li Shizhen read a lot of ancient medical books, and through clinical practice found that the ancient books of materia medica, "the number of items is both annoying, the name of the more mixed. Or a thing analyzed for two or three, or two things mixed for a product" ("Ming Wai Shi Ben Chuan"). In particular, many toxic drugs, but was considered to be "long service to prolong life", thus causing endless trouble. Therefore, he was determined to re-compile a book of materia medica. At the age of thirty-one, he began to brew, in order to "exhaustive search and collection", read a large number of reference books. The family collection of books read out, take advantage of the opportunity to practice medicine, to the township of the big families to borrow. Later, into the Wuchang Chu Wang Fu and the Beijing Imperial Hospital, read more books, simply become a "bibliophile". He described himself as "long delayed addiction to books, like eating sugar cane syrup" (the original preface to the Compendium of Materia Medica). In his biography of Li Shizhen, Gu Jingxing also praised him for "studying for ten years without leaving his house, and practicing all that he had learned". Indeed, he not only read more than 800 medical books and tens of thousands of volumes, but also many historical, geographical, and literary masterpieces, including the great works of history and history from Dunhuang, and the complete works of several great ancient poets. He also extracted a large number of verses on medicine. These verses gave him a lot of real and useful knowledge of medicine, and helped him to correct many fallacies in medicine of his predecessors. For example, in ancient medical books, the words "rushes and eiders" often appear. What do they refer to? Is there a difference? Pharmacists through the ages have different opinions, debate. Li Shizhen quoted Qu Yuan "Li Sao" in the "will compete with chickens and rushes for food," "will be flooded as if the water of the mallard," two lines, pointing out that the poet put "rushes" and He pointed out that the poet's use of the terms "rushing" and "eider" is a clear proof that they are not the same kind of birds. He also according to the poem on their different living environment, proving that "rushes" is a domestic duck, "eider" is a wild duck, different medicinal properties. Qu Yuan's poems and gifts have become the basis for Li Shizhen's eloquent examination of the name of the drug.
In the process of writing the "Compendium of Materia Medica", the most so that Li Shizhen headache is due to the name of the drug is mixed, often confused about the shape of the drug growth. The past book of materia medica, although repeated explanations, but because some authors do not have in-depth practical research, but in the books copied in the "paper guessing", so the more explained the more confusing, and contradictions multiply, so that people do not know what to say. For example, the drug Yuanzhi, the North and South Dynasties, the famous medicine Tao Hongjing said it is small grass, like ephedra, but the color green, white flowers, the Song Dynasty, Ma Zhi think it is like a big green, and blamed Tao Hongjing simply do not know Yuanzhi. Another example is the dog's spine a medicine, some say it is like the castor seed, some say it is like pulling the sparrow, some say it is like Guanzhong, the statement is very inconsistent. Similar to this case a lot, Li Shizhen had to put aside the pen again and again. How to solve these problems? In his father's revelation, Li Shizhen realized that "read a thousand volumes of books" is certainly necessary, but "walk ten thousand miles" is even more indispensable. So, he both "searching for a hundred", and "interviews with the four sides", in-depth practical investigation.
Li Shizhen put on straw shoes, back up the medicine basket, in the apprentice Pang Xian, son of Jianyuan accompanied, far away from the mountains and wilderness, visited the famous doctors and Confucian Confucianism, searching for folk remedies, observation and collection of drug specimens. He first interviewed in his hometown of Herb State. Later, he traveled many times. In addition to Hunan and Guangdong, but also to Jiangxi, Jiangsu, Anhui, many places. Tahe Mountain in Junzhou has also been there. Jiangxi Lushan, which is rich in medicinal herbs, and Nanjing's Mount Regency, Mount Maoshan, Mount Niushou, it is estimated that there are also his footprints. The descendants of this wrote "far from the poor and remote border of the production, the risk of exploring the foot of the Hua" of the poem, reflecting his long-distance trekking, the four sides of the life of the interviews.
Li Shizhen every place, to all kinds of characters request. Among them were those who picked medicine, those who farmed, those who fished, those who chopped wood, and those who hunted. Enthusiastically, they helped him learn about a wide variety of medicines.