Abstract: The exploration of Rhinoceros horn substitutes began in the Republic of China period. After the founding of the People's Republic of China, traditional Chinese medicine practitioners in Jiangsu and Guangdong were the first to use Bubalus horn instead of Rhinoceros horn to deal with the epidemic of infectious diseases and the shortage of Chinese medicinal materials, which drew widespread attention. In the 1970s, a nationwide collaboration was carried out on the research of Bubalus horn, achieving numerous results in the chemical analysis, pharmacological experiments and clinical trials of Bubalus horn. The standardization of local Chinese medicinal materials was realized, and Bubalus horn was included as a substitute for Rhinoceros horn in the 1977 edition of the Pharmacopoeia of the People's Republic of China. As a typical example of a substitute for traditional Chinese medicine, the research on Bubalus horn cannot be separated from the organic combination of basic research and clinical practice, as well as the integration of traditional Chinese medicine theory and modern science. It also cannot be separated from the arduous exploration of both Chinese and Western medical workers and provides an important reference for the transformation of the research path of contemporary traditional Chinese medicine.