Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.