Abstract: Chronic kidney disease is one of the major diseases threatening public health. Renal interstitial fibrosis (RIF) is a common pathological manifestation of various chronic kidney diseases in the end stage. However, the pathological mechanism of RIF remains to be clarified, and there is a lack of effective treatment for that. Increasing studies have shown that G2／M cycle arrest of renal tubular epithelial cells is an important event in the occurrence and development of RIF. In a variety of renal injury models, the causal relationship between G2／M cycle arrest of renal tubular epithelial cells and renal fibrosis has been found. Reversing G2／M cycle arrest has become a potential target to alleviate renal fibrosis. In addition, studies suggested that various pathways, including MAPK and autophagy, are closely related to G2／M cycle arrest, they affect the occurrence and progress of RIF collectively. This paper reviews the latest research on the involvement of G2／M cycle arrest in RIF, in order to provide ideas for the clinical diagnosis and treatment of chronic kidney disease and the development of new drugs.