In this study, we examined the potential effects of DMF on TGF-β-stimulated ECM production in vitro and unilateral urethral obstruction (UUO)-induced renal fibrosis in vivo, and elucidated its underlying molecular mechanisms which are associated with Nrf2-mediated inhibition of the TGF-β/Smad3 signaling pathway. This evidence concerns the gene SMAD3 and renal fibrosis.