Objective To explore the plague epidemiological trend of the nearly 25 years in Yushu Tibetan Autonomous Prefecture, Qinghai province, and to provide basis for implementation of the prevention and control measures. Methods Analyze the data of the human plague cases, plague surveillance and the plague foci research from 1990 to 2014 with the Excel software. Results There were 17 human plague outbreaks in 11 years out of 25 years from 1990 to 2014, 54 cases were reported, including 22 fatalities, the mortality was 40.74% (22/54). The patients were mainly distributed in the following 5 counties: Yushu, Nangqian, Qumalai, Chenduo and Zhiduo. Human plague cases occurred from May to October, the peak at July to October. The majority clinical cases were pneumonic plague (34/54, 62.96%). In 2004, pneumonic plague outbreaked in local area. Conclusion The plague epidemic situation in Yushu Tibetan Autonomous Prefecture, Qinghai province is still at high risk, the human plague in some area outbrook occasionally. So as to reduce human plague occurrence risk, while conducting the Marmot plague monitoring, the monitoring of Tibetan sheep plague should also be strengthened, and the comprehensive measures of plague prevention and control should be carried out.