〔Abstract〕 Objective To investigate the protective effect and mechanism of CP-25 on high insulin-induced podocyte injury. Methods Mouse podocyte were culturedin vitroand divided into blank control group,high-insulin model group,high insulin+CP-25(0.1、1、10 μmol/L) group and Metformin group.The effect of CP-25 on the proliferation of podocyte induced by high insulin was detected by CCK-8 method.The effect of CP-25 on glucose consumption induced by high insulin in podocyte was detected by GOD-POD method.Transwell method was used to detect the effect of CP-25 on the migration of podocyte induced by high insulin.Annexin V-FITC/PI double staining assay was used to detect the effect of CP-25 on high insulin induced apoptosis of podocyte.The effect of CP-25 on the expression of Nephrin protein in podocyte induced by high insulin was detected by Western blot. Results CCK-8 results showed that CP-25 could increase the proliferation capacity of high insulin induced podocyte.The results of GOD-POD showed that CP-25 could improve the glucose uptake ability of high insulin induced podocyte.Transwell experimental results showed that CP-25 could reduce the migration of podocyte induced by high insulin.Annexin V-FITC/PI double staining results showed that CP-25 could inhibit the apoptosis of pdocyte induced by high insulin.Western blot results showed that CP-25 could up-regulate the protein expression of Nephrin in podocyte induced by high insulin. Conclusion CP-25 can improve the injury of podocyte induced by high insulin,and the mechanism may be related to the expression of Nephrin.