Abstract: Objective To study the effect and its mechanism of SIRT1 on glucose-induced apoptosis of podocytes. Methods Human kidney podocytes were taken to treat with different methods, and divided into 5 groups:control group (culturing with the medium containing 5.6 mmol/L glucose), osmotic-NC group (culturing with the medium containing glucose 5.6 mmol/L+mannitol 25 mmol/L), HG group (culturing with the medium of 30 mmol/L glucose), HG+SIRT1 grouptransfecting with SIRT1 over-expression vector (pcDNA3.1-SIRT1)+culturing with the medium containing 30 mmol/L glucose, and HG NC grouptransfecting with the negative control vector (pcDNA3.1)+culturing with the medium containing 30 mmol/L glucose. The expression of SIRT1 in each group was detected by qRT-PCR and Western blot. Activities of SOD, CAT and GSH-Px, and levels of MDA and ROS in the cells from each group were detected with various corresponding kits. Cell apoptosis in each group were detected by flow cytometry. Western blot was used to detect changes of the expression of Cleaved Caspase-3 and Cleaved Caspase-9 in the cells from each group. Results The levels of SIRT1 mRNA and protein in podocytes cultured with high glucose decreased. After high glucose treatment of podocytes transfected with pcDNA3.1-SIRT1, the levels of SIT1 mRNA and protein in podocytes increased, the activities of SOD, CAT and GSH-Px decreased, the levels of MDA and ROS increased, the apoptotic rate increased, and the levels of cleaved caspase-3 and cleaved caspase-9 protein increased in podocytes treated with high glucose. Upregulation of SIRT1 could increase SOD, CAT, GSH-Px activities, decrease MDA and ROS levels, and decrease apoptosis and expression of cleaved caspase-3 and cleaved caspase-9 in podocytes under high glucose conditions. Conclusions Upregulation of SIRT1 can reduce the apoptosis of podocytes induced by high glucose, and the mechanism may be related to reduction of oxidative damage.