〔Abstract〕 Objective To investigate the role of miR-125b on hepatic angiogenesis, with the hope of providing new targets for the prevention and treatment of liver fibrosis. Methods The human hepatic sinusoidal endothelial cells were transfected with miR-125b mimics and inhibitors, and the mRNA and protein expression of vascular endothelial growth factor(VEGF), cluster of differentiation antigens 31(CD31), von Willebrand factor(vWF), collagen IV, and laminin(LN) were detected by qRT-PCR and ELISA, and the expression of nitric oxide(NO) was detected by fluorescent probe, scanning electron microscopy detected the alteration of the window holes on the surface of human hepatic sinusoidal endothelial cells, angiogenesis assay was performed to observe the neovascularization of each group, and dual luciferase reporter gene assay was performed to validate the targeting relationship between miR-125b and VEGF. Results qRT-PCR and ELISA showed that compared with the negative control group, the mRNA and protein expressions of VEGF, CD31, vWF, Collagen Ⅳ, and LN significantly decreased after miR-125b mimic transfection(P<0.05), while the mRNA and protein expressions of VEGF, CD31, vWF, Collagen Ⅳ, and LN were significantly increased after transfection with miR-125b mimics(P<0.05); fluorescent probe detection showed that compared with the negative control group, the average fluorescence of intensity expression NO decreased significantly(P<0.05), while the average fluorescence intensity expression of NO increased significantly after miR-125b inhibitor transfection(P<0.05); the number of fenestrations on the surface of human liver sinusoidal endothelial cells significantly increased after miR-125b mimic transfection(P<0.05), while the number of fenestrations on the surface of human liver sinusoidal endothelial cells decreased significantly after miR-125b inhibitor transfection(P<0.05); angiogenesis assay showed that compared with the negative control group, the number of angiogenesis significantly decreased after miR-125b mimic transfection(P<0.05), while the number of angiogenesis significantly increased after miR-125b inhibitor transfection(P<0.05); dual luciferase reporter gene assay showed that compared with negative control group, the expression of relative fluorescence intensity after transfection of miR-125b mimics in VEGF wild-typ significantly decreased(P<0.05), while the expression of relative fluorescence intensity after transfection of miR-125b mimics in VEGF mutant significantly decreased(P>0.05). Conclusion miR-125b can inhibit liver angiogenesis and thus play an anti-fibrosis role, which can provide a new reference for the prevention and treatment of chronic liver disease and the development of new drugs.