Objective To observe the effects of Tangshenning（TSN） on nephrin and synaptopodin of podocyte in diabetic kidney disease（DKD） mice.Methods The DKD mice model was established by feeding 8-week old KK-Ay mice with high-fat diet for 4 weeks and then randomly divided into model group,TSN group and Valsartan group.One more normal control group（NC） was the same age of C57 BL/6 J mice.TSN group were given TSN（raw herbs） with 20 g/（kg·d）to the stomach.Valsartan group was given Valsartan to the stomach with 10 mg/（kg·d）. NC group and model group were given equal amount of saline to the stomach.All mice were successively administrated for 12 weeks.After 0,4,8,and 12 weeks,urine was collected and urine protein was measured for 24 hours.After 12 weeks,blood was taken from the apex to measure the levels of serum creatinine and urea nitrogen.Kidney was removed for the ovbservation of pathological changes by HE,PAS,and Masson staining.The protein expression of nephrin and synaptopodin in podocytes was detected by immunohistochemistry,and mRNA expression of nephrin and synaptopodin in podocytes was detected by RT PCR.Results Compared with NC group,24 h proteinuria,serum creatinine and blood urea nitrogen was significantly increased（P<0.05） in model group.Compared with model group,24 h proteinuria,serum creatinine and blood urea nitrogen was significantly decreased（P<0.05） in TSN group and Valsartan group.Compared with NC group,the glomerular mesangial cells of model group were obvious increased,extracellular matrix obviously proliferated.Compared with the model group,the glomerular mesangial cells in TSN group and Valsartan group were obvious decreased,extracellular matrix obviously was alleviated.Compared with NC group,nephrin and synaptopodin of podocyte and mRNA level were significantly decreased in the model group（P<0.05）; Compared with the model group,nephrin and synaptopodin of podocyte and mRNA level were significantly increased in TSN group and Valsartan group（P<0.05）.Conclusion TSN can reduce proteinuria and ameliorate renal function of DKD mice,the mechanism of which may be related with increasing of nephrin and synaptopodin of podocyte and alleviating of podocyte damage.