Objective：To investigate the potential influence of thrombospondin⁃4(TSP⁃4)on the proliferation，apoptosis，oxidative stress and inflammatory response in podocytes stimulated by high glucose(HG)，thus revealing the function of TSP ⁃ 4 in the development of diabetic kidney disease(DKD). Methods：① Relative levels of TSP ⁃ 4 and signal transducer and activator of transcription3(STAT3)in HG⁃induced podocytes were examined by real⁃time quantitative PCR(qRT⁃PCR)and Western blot.②After intervention of TSP⁃4 in HG⁃induced podocytes，proliferative ability was examined by cell counting kit⁃8(CCK⁃8)and 5⁃Ethynyl⁃2’⁃ deoxyuridine(EdU)assay. The apoptosis and cell cycle distribution of podocytes were determined by flow cytometry. Relative contents of reactive oxygen species(ROS)，malondialdehyde(MDA)，superoxide dismutase(SOD)and catalase(CAT)were detected by commercial kits. In addition，the expression levels of inflammatory factors interleukin(IL)⁃1β，tumor necrosis factor(TNF)⁃α and IL⁃6 were measured by enzyme ⁃linked immunosorbent assay. ③The interaction between the transcription factor STAT3 and the promoter region of TSP ⁃ 4 was validated by chromatin immunoprecipitation(ChIP)and further confirmed by dual ⁃ luciferase reporter assay. Results：①TSP⁃4 and p⁃STAT3 were timE-dependently upregulated in HG⁃induced podocytes(P ＜ 0.05). ②Knockdown of TSP⁃4 could reverse the inhibited proliferation，apoptosis，oxidative stress and inflammatory response in HG⁃induced podocytes(P ＜ 0.05). ③ STAT3 could bind the promoter region of TSP⁃4，thus inducing the transcription，and potitively regulating the TSP⁃4 promoter activity.Conclusion：Knockdown of TSP ⁃ 4 alleviates HG ⁃induced apoptosis，oxidative stress and inflammatory response in podocytes，thus showing a protective effect on podocytes. Transcription factor STAT3 has positive function to the promoter activity of TSP⁃4.