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Background: Diabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by interstitial and glomeruli fibrosis.Epithelial-to-mesenchymal Transition (EMT) plays an important role in DN.Tong xinluo(TXL)-a Traditional Chinese Medicine, has been used in China with established therapeutic efficacy in patients with DN.Methods: We investigated the protective role of TXL both in vivo and vitro.KK-Ay mouse was selected as model for the evaluation of pathogenesis and treatment in diabetic nephropathy.In vitro, TGF-β1 was used to induce EMT.Western Blotting (NB), Immunocytochemistry (ICC) and Real Time-Polymerase Chain Reaction (RT-PCR) were applied to detect the changes of EMT makers in vivo and in vitro, respectively.Results: We found that TXL successfully attenuated EMT both in vivo and in vitro.To investigate the mechanisms involved in TXLs protective effects, we found that TXL greatly reduced TGF-β1 and its downstream protein smad3/p-smad3 expression, meantime, TXL restored the expression of smad7.Conclusion: In summary, our study demonstrates that Traditional Chinese Medicine TXL inhibiting TGF-β1-induced Epithelial-to-mesenchymal Transition in diabetic nephropathy, which may account for the therapeutic efficacy in TXL-mediated renoprotection.