Objective To observe the effect of Tangluoning（TLN）on oxidative stress and apoptosis in high glucose incubated Schwann cells with Keap1/Nrf2/Bcl-2 signal pathway as breakthrough point according to the key pathogenesis of oxidative stress in the prevention and treatment of diabetic peripheral neuropathy（DPN）.Methods 150 mmol/L glucose incubated Schwann cells（SCs）were used as cell models followed by setting control group,high glucose group,ALA serum group and TLN serum group,and after intervention for 36 hour（h）,flow cytometry were used to analyze superoxide radical（ROS）and apoptosis.JC-1 staining was used to observe mitochondrial membrane potential（MMP）.High content analysis（HCA）and Western blot analysis were used to assess the changes of the expression of Keap1,Nrf2,HO-1 and γGCS in Keap1/Nrf2 pathway and Bcl-2 mediated apoptosis related protein including Bcl-2,Bax,Cyto C and Caspase-3.Results After incubated with high glucose for 36 h,apoptosis and ROS levels were increased but MMP decreased in high glucose group compared with the control group（P<0.01）.Apoptosis and ROS levels were decreased and MMP increased in TLN serum group compared with high glucose group（P<0.05 or P<0.01）.The results of HCA and Western bolt analysis showed that Keap1,Nrf2,HO-1 and γGCS were increased in high glucose group compared with the control group（P<0.01 or P<0.05）and Keap1,Nrf2,HO-1 and γGCS further increased in TLN group compared with high glucose group（P<0.01 or P<0.05）.Bcl-2,Bax,Cyto C and Caspase-3 were increased in high glucose group compared with control group（P<0.01 or P<0.05）and Bcl-2 expression further increased but Bax,Cyto C and Caspase-3 decreased in the TLN group compared with the high glucose group（P<0.01 or P<0.05）.Conclusion TLN can inhibit the oxidative stress and apoptosis of Schwann cells in high glucose environment,and it is related with the up-regulation of protein expression in Keap1/Nrf2 pathway against antioxidative stress,and regulation of the expression of Bcl-2-related apoptotic pathway protein to inhibit cell apoptosis.