Abstract: Objective To investigate the effect of capsaicin on high-salt induced renal tubulointerstitial fibrosis in Wistar rats and its possible mechanism. Methods Thirty-six male Wistar rats were randomly divided into three groups:normal diet groupn=12,regular salt diet（0.5% salt）,high salt diet groupn=12,high salt diet（4%salt）,and capsaicin groupn=12,high salt（4% salt）+0.02% capsaicin diet. Tail arterial systolic blood pressure was measured by intelligent noninvasive blood pressure monitor every 4 weeks. The serum creatinine,24-hour urinary protein,24-hour urinary retinol binding protein（URBP）and Tamm-Horsfall（TH）glycoprotein were measured at the 24 th week. The morphological changes of renal medulla were observed by HE staining,and renal tubulointerstitial fibrosis was observed by Masson staining. In addition,the protein expressions of transient receptor potential vanilloid 1（TRPV1）,transforming growth factor-β₁（TGF-β₁）,p-Smad2/3,α-smooth muscle actin（α-SMA）,vimentin,collagen typeⅠ（ColⅠ）and collagen typeⅢ（ColⅢ）in the renal medulla were measured by immunohistochemistry and Western blotting. Results Compared with the normal diet group,the blood pressure（138.9±6.8）vs（107.8±7.6）mm Hg,P＜0.05,fibrosis index of renal interstitium（23.55±2.23 vs 11.30±1.26,P＜0.05）,24-hour urinary protein,24-hour URBP were significantly increased,while 24-hour urinary TH glycoprotein was decreased in the high salt group. The protein expressions of TRPV1 was lower,while expression of TGF-β₁,p-Smad2/3,α-SMA,vimentin,ColⅠand ColⅢin the renal medulla were higher in the high salt group than those in the normal diet group. Compared with the high salt group,the blood pressure （119.5±8.3）vs（138.9±6.8）mm Hg,P＜0.05,fibrosis index of renal interstitium（15.65±1.72 vs 23.55±2.23,P＜0.05）,24-hour urinary protein,24-hour URBP were decreased,while 24-hour urinary TH glycoprotein and the protein expression of TRPV1 was significantly increased,the protein expressions of TGF-β₁,p-Smad2/3,α-SMA,vimentin,ColⅠ and ColⅢ were significantly decreased（all P＜0.05）in the capsaicin group. Conclusion Renal tubulointerstitial fibrosis（RIF）could be induced by long-term high salt diet in Wistar rats,and capsaicin improved high-salt induced renal injury by inhibiting renal tubulointerstitial fibrosis,probably via activating TRPV1.