〔Abstract〕 Objective To investigate the role and possible mechanism between phosphatidylinositol-3-kinase/protein kinase B( PI3 K/AKT) pathway and transient receptor potential cation channel protein 6( TRPC6) in the process of angiotensin Ⅱ( Ang Ⅱ)-induced glomerular podocyte injury. Methods Mouse glomerular podocytes were cultured in vitro and treated with Ang Ⅱ,Losartan,PI3 K/AKT pathway inhibitor( LY294002),TRPC6 channel blocker( SKF96365). The cells were divided into blank control group and Ang Ⅱ group,Ang Ⅱ + Losartan group,Losartan group,Ang Ⅱ + LY294002 group,LY294002 group,Ang Ⅱ + SKF96365 group,SKF96365 group.The qRT-PCR was used to detect the changes of TRPC6 mRNA in each group. Western blot was used to detect the changes of AKT,phosphorylated protein kinase B( p-AKT),and TRPC6 protein expression in each group. The apoptosis of podocytes was detected by Hoechst 33258 staining. Results Compared with the blank control group,the AKT phosphorylation level of the Ang Ⅱ group decreased,the expression of TRPC6 increased,and the apoptosis of podocytes increased( P<0. 05). Compared with the Ang Ⅱ group,the AKT phosphorylation level of the Ang Ⅱ + SKF96365 group increased,the expression of TRPC6 decreased,and the apoptosis of podocytes decreased( P<0. 05); the AKT phosphorylation level of the Ang Ⅱ + LY294002 group decreased,and the apoptosis of podocytes increased( P<0. 05); the AKT phosphorylation level of the Ang Ⅱ + Losartan group increased,the expression of TRPC6 decreased,and the apoptosis of podocytes decreased( P<0. 05). Conclusion Ang Ⅱ may induce podocyte injury by activating the TRPC6 channel and thereby inhibiting the activation of PI3 K/AKT pathway.