Abstract: Objective To investigate the effect of Fushengong Decoction on the expression of nephrin mRNA in renal tissue of rats with chronic renal failure (CRF). Methods Fifty five male SD rats were randomly divided into five groups: control group, CRF model group, and low, medium and high Fushengong Decoction dose groups. Rats in control group were fed with standard chow, while the other four groups were fed with adenine to make CRF. The rats in control group received intra-gastric normal saline (NS) of 20 mL/(kg·d) for 30 d, while those in low, medium and high Fushengong Decoction dose groups received Fushengong Decoction at the dose of 4 g/kg, 8 g/kg and 16 g/kg respectively, once a day for 30 d. After that, 24 h urinary protein in urine was measured, blood urea nitrogen (BUN) and serum creatinine (SCr) were detected. Histomorphology of glomerulus were studied by HE staining, and the expression of nephrin were detected by immunohistochemistry and RT-PCR. Results Compared to the control group, the levels of 24 h urinary protein, BUN and SCr increased significantly (P<0.05) and the expression of nephrin protein and mRNA decreased significantly (P<0.05) in CRF model group. The renal interstitium showed fibrotic lesions in model group. The levels of 24 h urinary protein, BUN and SCr decreased significantly after the treatment of Fushengong Decoction (P<0.05), while the expression of nephrin protein and mRNA increased significantly (P<0.05). Conclusion Fushengong Decoction could reduce urinary protein and relieve renal damage in rats with CRF by improving the expression of nephrin and reducing the injury of podocytes.