〔Abstract〕 Objective To study the protective effect of berberine(BBR) on podocytes in high glucose environment and to discuss its mechanism. Methods The exponential growth stage of the glomerular podocyte was selected. The podocyte were divided into 5 groups, including normal control group, high-glucose model group and BBR was given in concentrations of 30, 60 and 90 μmol/L. Annexin FITC/PI double staining was used to detect the apoptosis rate of podocytes. High-intension imaging system was used to detect cell proliferation,podocyte migration was measured by transwell and cell scratch assay,Western blot detected the expression of AKT/NF-κB signaling pathway related proteins,apoptotic protein Bim,and the podocyte marker proteins WT-1,Podocin and desmin. Results Compared with the normal group,the results of Annexin FITC/PI double staining showed that the apoptosis rate of podocytes in the high glucose group increased( P<0. 01); The high-content imaging system showed that the number of podocytes in the high glucose group decreased( P<0. 01); Transwell showed that the number of podocytes migrate ability increased in the high glucose group( P<0. 01); The cell scratch showed that the scratch healing rate of the high glucose group increased( P<0. 01); Western blot showed that the expression levels of p-AKT,p-p65,p-IκBα,Bim,and desmin protein in the podocytes of the high glucose increased( P<0. 01),and the expression of WT-1 and Podocin proteins decreased( P<0. 01). Compared with the high glucose group,the apoptosis rate of podocytes decreased after add BBR( P<0. 05); the number of podocytes increased in the different concentrations of BBR( P<0. 01); the number of podocyte migration was lower( P<0. 05); Scratch healing rate decreased( P<0. 01); In addition,BBR reduced the protein expression levels of p-AKT,p-p65,p-IκBα,Bim and desmin( P<0. 05),the expression level of WT-1 and Podocin protein increased( P<0. 01). Conclusion BBR may improve the podocyte injury,inhibit the podocyte apoptosis,and weaken the podocyte migration ability induced by high glucose through regulating AKT/NF-κB signaling pathway.