【Abstract】Objective To investigate the effect of total saponins of momordicq charantia on Smad3 protein and Smad7 protein expression in rats with adriamycininduced nephropathy, and provide reference for the development of Chinese herbal medicine. Methods Fifty male SpragueDawley rats were randomly divided into normal group, model group and total saponins group. Except the control group， other groups were received intravenous injection of doxorubicin 62 mg/kg. After the success built the model, the normal group and the model group were given normal saline, and the total saponins of momordica charomdia were given 10mg/kg /d, 20mg/kg/d, 40mg/kg/d, 8 weeks. The blood useanitrogen (Bun) and serum creatinine (Cr) were measured. The renal tissues were detected by HE staining. The expression of Smad3 and Smad7 were detected with Western blot, RTPCR and Immunohistochemistry. Results Compared with the normal group, after 8 weeks of treatment, 24 hours urine protein of the model group and the total saponins groups were significantly increased compared with the model group. 24 hours urine protein of the three treatment groups were significantly lower than that of the model group. The total saponins can significantly reduce the Bun and Cr. Compared with the normal group, the model group and total saponins group showed significant glomerular sclerosis accompanied by significant renal cell injury (P＜0.05). Compared with the normal group, Smad3 was significantly increased in the model group (P＜0.05), and the levels of Smad7 were significantly decreased (P＜0.05). The expression of Smad7 protein was significantly increased (P＜0.05). Conclusion The total saponins of momordica charantia can significantly improve the glomeruli and renal tubular injury, decrease the proteinuria for 24 hours and regulate Bun and Cr, which can regulated the Smad3 and Smad7 protein.