Objective    To investigate the effect of Cordyceps sinensis on renal fibrosis and its possible mechanism.  Methods    Thirty Sprague - Dawley rats were randomly divided into three groups: Sham operation group (Sham，n＝10), 5/6 subtotal nephrectomy group (SNx, n＝10), and 5/6 subtotal nephrectomy treated with Cordyceps sinensis group (CS, n＝10). Body weights were assessed and 24 - hour urine excretion was collected before and every four weeks after surgery. Rats were sacrificed at 12 weeks after surgery. Blood samples were taken for biochemical study, and kidney tissues were used for HE and Masson stains to assess histological changes. Immunohistochemical staining was used to detect the expression of transforming growth factor β1 (TGF-β1) and its receptors of type Ⅰ(TβRⅠ), type Ⅱ (TβRⅡ). Immunofluorescence was used to detect E-cadherin and α-SMA. The relative protein level of TGF-β1, TβRⅠ, TβRⅡ, p-Smad2/3, Smad7, E-cadherin, α-SMA were examined by Western blotting.  Results    CS group had higher body weights and lower urinary protein, BUN and Scr level compared with SNx group. Glomerulosclerosis index and tubulointerstitial injury score were significantly reduced in CS group compared with those in SNx group (all P＜0.05). The protein expressions of TGF-β1,TβRⅠ, TβRⅡ, p-Smad2/3 were decreased in CS group compared with those in SNx group (all P＜0.05). CS treatment up-regulated the expression of E-cadherin, Smad7 and down - regulated the expression of α - SMA compared with that in SNx group (all P＜0.05).  Conclusion    Cordyceps sinensis has inhibitory effect on renal fibrosis in 5/6 subtotal nephrectomy rat model, which might be related with the suppression of TGF-β1 signal pathway.