In the present study, we demonstrated that FXR activation suppresses kidney fibrosis by downregulating Smad3 expression in vitro and in vivo, suggesting that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibrosis. The gene discussed is NR1H4; the disease is renal fibrosis.