Objective: To investigate the effects of Carboxypeptidase E (CPE) on the cell proliferation, cell cycle and apoptosis of mice mesangial cells (MMC) cultured in high glucose. Methods: The CPE gene fragment was amplified by PCR and inserted into the expression vector pcDNA3.1 plasmid to construct the recombinant plasmid pcDNA3.1-CPE. The plasmid was transfected into MMC, and the expression of CPE-tagged protein, proliferation marker CyclinD1, PCNA and apoptosis markers Caspase-3 were detected by Western blotting; plate cloning ,CCK-8 method and flow cytometry were used to detect the effect of overexpressed CPE on the proliferation, cell cycle and apoptosis of MMC cells cultured in high glucose. Results: pcDNA3.1-CPE over-expression plasmid were successfully transfected into MMC. plate cloning and CCK-8 showed that overexpression of CPE could inhibit the proliferation of MMC. Flow cytometry showed that compared with the control group, CPE over-expression significantly promoted the cell apoptosis, G1 phase cells increased significantly as well as S phase cells decreased obviously, the difference was statistically significant (P<0.01). Conclusion: CPE can inhibit the proliferation of MMC cultured in high glucose and induce the cell apoptosis.