Significance statement
Tubulointerstitial fibrosis is an unavoidable consequence of advancing chronic kidney disease (CKD) and imposes a substantial global health burden. However, few effective therapeutic agents are available at present. The present study investigated the ameliorative effects of icariin on tubulointerstitial fibrosis (TIF) both in vivo andin vitro , and demonstrated that icariin inhibited inflammation and oxidative stress, at least partially, through improving Nrf2 activity and subsequent mitochondrial function, and eventually mitigated TIF and preserved renal function, suggesting that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.