Abstract: Leptospirosis is a zoonotic and natural focal disease caused by pathogenic Leptospira. With global climate warming and process of urbanization, pathogenic Leptospira is undergoing adaptive changes in order to adapt to the environment. Recent rapid advances in various molecular typing and omics techniques have made people learn more about the genetic diversity, molecular evolution, and pathogenic mechanisms of this pathogen. This study introduces the incidence trend of leptospirosis and molecular typing methods of the pathogen, then summarizes the progress in the research of molecular evolution and pathogenic mechanisms of Leptospira to provide reference for the molecular epidemiological surveillance for leptospirosis and the development of new vaccines for the prevention of leptospirosis.