Objective：To study the effect and mechanism of cantharidin（protein phosphatase 2A inhibitor） on the protection of pancreatic β-cell’s death and dysfunction. Methods：Twenty type 1 diabetic mice induced by low dose streptozotocin（STZ） were randomly assigned into cantharidin-treated group（n=10） and diabetes mellitus group（n=10）. Ten healthy mice were as normal control. The level of fasting blood glucose（FBG） was continuously detected. In the end, the level of fasting serum insulin（FINS） was measured and the morphology of pancreas was observed under optical microscope with HE staining. Results：The level of FBG in cantharidin-treated group was obviously lower than diabetes mellitus group（P < 0.05）. The level of FINS in cantharidin-treated group was significantly higher than diabetes mellitus group（P < 0.01）. Compared with diabetes mellitus group，the volume and cell number of islets in cantharidin-treated group were increased significantly. Conclusion：Cantharidin could obviously protect STZ-induced diabetes on mice through improving structure and function of survival islets and enhancing the insulin secretion of pancreatic β-cells.