〔Abstract〕 Abstract Objective To investigate the role of AdipoRon , an adiponectin receptor agonist , in treatment of carbon tetrachloride (CCl4 ) induced liver fibrosis mice model and the mechanisms . Methods Forty mice were randomly divided into control group , model group , L- AdipoRon group and H-AdipoRon group , with 10 mice in each group . Hepatic fibrosis was induced by intraperitoneal injection of CCl4 solution . The mice in L- and H-AdipoRon groups were given 100 mg/kg and 200 mg/kg AdipoRon by gavage , respectively . The activities of serum aspartate amin- otransferase (AST) and alanine aminotransferase (ALT) were detected by biochemical method . Liver histopatho- logical changes and fibrosis were detected by HE staining , Masson staining and Sirius scarlet stain . The protein ex- pression levels of Collagen I , α-smooth muscle actin ( α-SMA) , matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase inhibitor 1 (TIMP-1) in mice liver were detected by Western blot. Lipid deposition in liver were detected by oil red O staining. The percentage (% ) of CD68 + iNOS + positive M1-type macrophages in the liver were detected by immunofluorescence . The expression levels of fatty acid synthetase (Fasn) , stearoyl-CoA desatu- rase 1 (Scd1) , fatty acid transporter (Cd36) , peroxissome proliferator activated receptor-α(Pparα) and carnitine palmitoyl transferase 1 α (Cpt1α) in mice liver tissues , as well as M1 macrophage-related genes interleukin-6 (IL- 6) and tumor necrosis factor-α(TNF-α) and M2 macrophage-related genes arginase 1 ( Arg1) , Chil3 chitinase- like 3 (Ym-1) were detected by RT-qPCR assay . Results Compared with model group , in low-dose AdipoRon group and high-dose AdipoRon group , serum ALT and AST activities significantly decreased (P < 0. 05) ; liver tis- sues structure were damaged , liver cells degeneration and inflammatory cells infiltration were improved; collagen fi- ber deposition was also significantly reduced; the relative expression levels of Collagen I , α-SMA and TIMP-1 pro- teins were significantly down-regulated (P < 0. 05) , while the relative expression levels of MMP-1 protein were sig- nificantly up-regulated (P < 0. 05) ; the lipid droplets deposition in livers were significantly reduced . The relative Fasn , Scd1 and Cd36 mRNA expression levels in liver tissues were significantly down-regulated (P < 0. 05) , and the relative Pparαand Cpt1 αmRNA expression levels were significantly up-regulated (P < 0. 05) ; the percentage (% ) of CD68 + iNOS + positive M1-type macrophages significantly decreased (P < 0. 05) ; the relative IL-6 and TNF-αmRNA expression levels significantly decreased (P < 0. 05) , the relative Arg1 and Ym-1 mRNA expression levels were significantly up-regulated ( P < 0. 05 ) . In addition , the improvement effects of high-dose AdipoRon group were better than those of low-dose AdipoRon group ( P < 0. 05) . Conclusion AdipoRon can improve the disorder of lipid metabolisms , inhibit the M1 type macrophages polarization , and improve the liver fibrosis in CCl4 - induced liver fibrosis mice model .