Accordingly, we can conclude that piperine possesses a potential therapeutic effect on hepatic fibrosis by restoration of liver enzymes, AST and ALT levels and through targeting the TGF/Smad signaling pathway resembled in the decrease in expression levels of TGF-β, Smad-3, and miR-17-5p and the increase in the expression level of the negative feedback inhibitor Smad-7, in addition to regression of ECM accumulation by reducing α-SMA deposition and collagen-α1 relative expression. This evidence concerns the gene TGFB1 and Hepatic fibrosis.