Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPAR gamma) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPAR gamma mRNA degradation, but the mechanism by which miRNAs regulate PPAR gamma in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3'-untranslated region (3'-UTR) of PPAR gamma mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPAR gamma expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPAR gamma expression by targeting the 3'-UTR of PPAR gamma mRNA in rat HSC-T6 cells. Transforming growth factor-beta 1 (TGF-beta 1) may mediate miR-130a and miR-130b overexpression, PPAR gamma downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPAR gamma in liver fibrosis. (C) 2015 Elsevier Inc. All rights reserved.