Objective:To observe the effect of Tangshenning (TSN) on renal pathology and podocyte apoptosis in diabetic nephropathy (DN) mice. MethodsThe DN model was established by using KK-Ay mice, and the successful modeling KK-Ay mice were randomly divided into model (DN) group, TSN group and valsartan(VST) group. In addition, the same number of C57BL/6J mice was selected as the normal control (NC) group. The mice in the TSN group were fed with TSN 20 g kg-1·d-1, VST group with VST 10 mg kg-1· d-1 and the normal control and DN groups with the same dose of distilled water. The duration of intragastric administration was 12 weeks. 24-hour urinary protein was detected at 0,4, 8 and 12 weeks after intragastric administration, and blood samples from the apical heart were taken to detect the levels of serum creatinine and urea nitrogen after 12 weeks. The pathological changes of kidneys were observed by HE, Masson and PAS staining. The expression of Caspase-3 protein in podocytes was detected by immunohistochemistry and RT-PCR, and the apoptosis of podocytes was observed by TUNEL staining.  Results:① Compared with the NC group,24-hour urinary protein,serum creatinine and urea nitrogen in the DN group were significantly increased (P<0.05); compared with the DN group,24-hour urinary protein,serum creatinine and urea nitrogen in the TSN and VST groups were significantly decreased (P<0.05). ②Compared with the NC group, the glomerular mesangial cells in the DN group increased and the extracellular matrix proliferated; compared with the DN group, the glomerular mesangial cells decreased and the extracellular matrix proliferation decreased in the TSN group and VST group. ③Compared with the NC group, the expression of Caspase-3 protein and mRNA in podocytes in the DN group were significantly up-regulated (P<0.05), while the expression of Caspase-3 protein and mRNA of podocytes in the TSN and VST groups were significantly down-regulated.④ Compared with the NC group,the number of podocyte apoptosis was significantly increased in the DN group (P<0.05) and that in the TSN and VST groups was significantly decreased than that in the DN group (P<0.05).  Conclusion:TSN can reduce proteinuria and improve renal function in mice with diabetic nephropathy, and its mechanism may be related to its improvement of renal pathology and reduction of podocyte apoptosis.