Objective: Overexpression of microRNA-21 (miR-21) has been well-recognized during fibrosis in a wide range of tissue types through regulation of fibrogenesis via diverse pathways.Curcumin exhibits antifibrotic effects in various organs.We and others have previously demonstrated that curcumin has positive effects on the protection against fibrosis.However,the effect of curcumin on miR-21 expression has not been reported.Methods: In this study,transforming growth factor-β1 (TGF-β1)-stimulated rat renal fibroblast cells (NRK-49F) were transfected with miR-21 inhibitors,then the expression of Smad3,α-smooth muscle actin (α-SMA),type Ⅰ collagen (COL1A1),and type Ⅲ collagen (COL3A1) was determined using quantitative real-time-PCR (qRT-PCR) and west blot analysis.The effect of curcumin on production of the extracellular matrix was evaluated using immunofluorescence,qRT-PCR,and west blot analysis.Results: TGF-β1 stimulation upregulated the expression of miR-21 and induced fibrogenesis in NRK-49F cells.Transfection with miR-21 inhibitors selectively decreased smad3 activity,and noticeably reduced the expression of α-SMA,COL1A1,and COL3A1.Curcumin treatment significantly inhibited the expressions of smad3,α-SMA,COL1A1,COL3A1,as well as miR-21 expression in NRK-49F cells in a dosedependent manner.Conclusion: Curcumin exerted its anti-fibrotic effects by targeting the TGF-β1/smad3 signaling pathway and suppressing miR-21 expression,thereby provides novel insight in the protective effects of curcumin against fibrosis in various organs.