The main stages of the creation of the oldest Russian department of pathophysiology at the Sechenov University are presented in this article. The authors provide information on the origin of pathophysiology as an independent educational discipline and scientific specialization, and on the prerequisites for the creation of a separate pathophysiology department (at that time, general pathology) at Imperial Moscow University (IMU) in the second half of the 18th century. The connection between the work of the first Russian professor of the medical faculty, S.G. Zybelin, and the initial elements of pathophysiology as a science and teaching subject at IMU are elucidated