The replicative senescence of mesenchymal stem cells(MSC) during the in vitro expansion limits their use in the research and treatment of many disease. Also, MSC senescence may promote the individual senility, hypofunction of tissue and organ, and tumorigenesis. Thus, in order to better understand the senescent mechanism and delay the senescence, even reverse MSC senescence, the roles of signaling pathway, such as Wnt/β-catenin, MAPK/ERK, PI3K/AKT and ROS-related signaling pathway during the MSC senescence all were reviewed, so as to can deepen the under-standing of MSC senescence and provide a new thinkings for delaying, even reversing the MSC senescence.