Hepatic fibrosis is a reversible scaring response to chronic liver injury. MicroRNA (miR)-129-5p might regulate fibrosis-related gene expression. This study is performed to decipher, potential of miR-129-5p to influence the progression of hepatic fibrosis in a carbon tetrachloride (CCl₄) rat model. Rat hepatic fibrosis was successfully established by subcutaneous injection of 50% CCl4. RT-qPCR revealed that miR-129-5p was poorly expressed and PEG3 was highly expressed in hepatic fibrosis tissues. As reflected by dual-luciferase reporter gene assay, miR-129-5p targeted and reduced the expression of PEG3. Thereafter, miR-129-5p antagomir or short hairpin RNA against paternally expressed gene 3 (PEG3) was adopted for gain- and loss-of-function assay to determine the molecular regulatory mechanism of miR-129-5p. Moreover, we detected the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins and apoptosis-related factors, and made a serological analysis of the rat serum samples. Results showed that upregulated miR-129-5p or downregulated PEG3 led to reduction of the histological changes of liver cirrhosis and lowered the apoptosis rate, via downstream effects on the NF-κB signaling pathway. Thus, the hepatic fibrosis induced by CCl₄ can be rescued by upregulated miR-129-5p or downregulated PEG3 expression.