Abstract: Public health institution is an important part of modern urban management system in Guangzhou, and historicism provides a theoretical perspective for us to understand the institutional logic of its development and changes. The changes of public health system in Guangzhou can be divided into two periods: the path locked-in of traditional urban health institution and the sudden change of modern public health institution. The institution design of traditional urban health management was not perfect, and it gradually failed to adapt to social development. However, due to its advantages in time series and continuous reinforcement in governance, it caused path dependence in urban health management. The great plague outbreak in 1894 became a critical juncture in the changes of public health institution in Guangzhou. In order to cope with the severe crisis caused by the plague, the government began to take charge of urban public health management and make a series of breakthroughs in modern Guangzhou's public health institution. Through the analysis of the institutional environment, actors and institutional arrangement of the two periods, the track of the changes of public health system in modern Guangzhou can be clearly seen. The changes of public health system dominated by the government have highlighted the characteristics of national management and achieved urban sanitation to some extent.