〔Abstract〕 Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora. Methods The 25 SD rats were randomly divided into five groups: the Sham group, the BDL group, the negative control adenovirus(NC adv) group, the miR-199a-5p adv group and the miR-199a-5p sponge adv group. The pathological changes of liver tissue and the degree of liver fibrosis were observed by HE, Masson and Sirius Red staining. The levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin(TBIL) and direct bilirubin(DBIL) in serum of rats were determined by a fully automatic biochemical analyzer. The mRNA expression level of miR-199a-5p in liver tissue of rats was detected by qRT-PCR. The protein expression levels of α-smooth muscle actin(α-SMA) and collagen type 1 alpha 1(COL1A1) in liver tissue of rats were detected by double immunofluorescence staining and Western blot experiment. Rat feces were collected for 16S rRNA high-throughput sequencing. Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P<0.01). Compared with the NC adv group, the degree of liver injury and collagen deposition were relatively serious, the levels of AST, ALT, TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(allP<0.05). However, the results of miR-199a-5p sponge adv intervention were opposite(allP<0.05). The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota, changed composition of intestinal microbiota, while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(allP<0.05). Conclusion miR-199a-5p promotes liver fibrosis of BDL rats, and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.