Objective To explore the inhibitory effect of Zhenqi Fuzheng granules on angiogenesis in hepatocellular carcinoma (HCC) model rats and the possible mechanisms. Methods Wistar rats were divided into the control, model [discontinuous low-dose (Diethyl ammonium nitrite, DEN) induction method , Zhenqi Fuzheng granule (2. 62 g / kg), si-miR-200c (20 pm), and Zhenqi Fuzheng granule + si-miR-200c groups ( n= 12 rats per group) and were treated for 8 weeks. Hematoxylin and eosin staining was used to observe the pathomorphological changes in the rat liver tissues. Serum vascular endothelial growth factor ( VEGF ), alanine aminotransferase ( ALT ), and aspartate aminotransferase (AST) levels were detected via enzyme-linked immunosorbent assay ( ELISA). Real-time fluorescence quantitative PCR was used to detect miR-200c expression in the liver tissues; zinc finger protein ( ZEb-2) and VEGF protein were detected via western blot, and the positive expressions of ZEb-2, VEGF and microvessel density (MVD) were detected via immunohistochemistry. Results Compared with the control group, VEGF, ALT and AST levels were increased in the model group, and the model group livers contained more polymorphic and necrotic cells and showed decreased miR-200c expression, increased ZEb-2 and VEGF expressions, and increased ZEb-2, VEGF and MVD positivity rates (allP< 0. 05). Compared with the model group, the Zhenqi Fuzheng granule group had lower VEGF, ALT and AST levels, reduced cell deformation, higher cancer cell differentiation, increased miR-200c expression, decreased ZEb-2 and VEGF expressions, and decreased ZEb-2, VEGF and MVD positivity rates. The si-miR-200c group presented increased VEGF, ALT and AST levels, increased cell carcinogenesis, decreased miR-200c expression in the liver, increased ZEb-2 and VEGF expressions, and increased ZEb-2, VEGF and MVD positivity rates ( allP< 0. 05). VEGF, ALT and AST levels in the Zhenqi Fuzheng granule + si-miR-200c group were lower than those in the si-miR-200c group, while the ZEb- 2 and VEGF expressions and the ZEb-2, VEGF and MVD positivity rates were lower, and the miR-200c expression was higher than that of the si-miR-200c group (allP< 0. 05). Conclusions Zhenqi Fuzheng granules inhibited angiogenesis and alleviated HCC development in rats. Its mechanism may be related to upregulating miR-200c expression and downregulating ZEb-2 protein expression.