The plague is a zoonotic disease caused by Yersinia pestis (Y. pestis). This bacterium Y. pestis has caused three deadly pandemic plague worldwide. Considering of expanding natural foci and frequent population turnover, prevention and control of plague is still grim. In this review, we mainly summarize the research progress on the virulence factors of Y. pestis, the mechanism of invasion, the intracellular replication and the dissemination mechanism in the host.