Objective To retrospectively analyze two human plague epidemics in Sichuan province, China, from 1999 to 2017, and to provide a scientific basis for response to and disposal of human plagues. Methods Data were collected from the epidemiological investigation reports, the reports of biochemical tests for strain identification, the reports of tests for identification of strain virulence, and the literature related to the above two plagues. Microsoft Excel 2007 was used to collate, compare, and statistically analyze the data on epidemiology, clinical manifestation, laboratory diagnosis, and epidemic disposal. Results The two public health emergency events were caused by Yersinia pestis in the blood directly via the wounds of the herdsmen while peeling/eating naturally dead animals. Five people died from human plague in Gayi town, Shiqu county, Sichuan, in 1999, and one died from human plague in Cunge town, Litang county, Sichuan, in 2012. Conclusion The two human plague epidemics have brought great impacts on the health of local residents, and a summary of treatment experience of human plague helps to deal with the development of human plague in timely, effective, and scientific manner.