To study the protective effect and mechanism of the total saponins from the roots of Clematis florida Thunb. var. plena on CCl₄-induced hepatic fibrosis in mice.Fifty ICR male mice were randomly divided into normal group,model group,bifendatatum group and total saponins of Clematis florida Thunb. var. plena (SCFP) low and high dose groups.Except for the normal group,the mice in the other groups were injected with CCl₄ solution by intraperitoneal injection.Except for the model group and the normal group,each drug group was given the same dose of 0.1% CMC-Na aqueous solution by intragastric administration.After the last administration,blood and liver tissue of mice were collected.HE and Masson staining were used to observe the histopathological changes of the liver in each group;the contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and the expression levels of human collagen type Ⅰ (Col Ⅰ) and human collagen type Ⅲ (Col Ⅲ) in serum were detected by biochemical kits and ELISA kits;the contents of malondialdehyde (MDA),superoxide dismutase (SOD),glutathione (GSH) and nitric oxide (NO) in liver;the expression levels of transforming growth factor-β (TGF-β1) and α-smooth muscle actin (α-SMA) in the liver of mice were detected by immunohistochemical staining;the protein expressions of TGF-β1,matrix metalloprotein-9 (MMP-9),α-SMA and SMAD2 in the liver were detected by Western blot.The results showed that compared with the model group,the SCFP group decreased the degree of liver tissue damage,the degree of hepatocyte degeneration,and significantly decreased collagen deposition,and the serum ALT and AST levels of the mice in the SCFP group was significantly decreased,and the serum fibrosis-related factors Col I and Col Ⅲ was significantly decreased;the expressions of TGF-β1,MMP-9,α-SMA,TGF-β1 and SMAD2 in liver tissue were significantly decreased;the antioxidant indexes SOD and GSH in liver increased significantly,while MDA and NO decreased significantly.The results of this study show that SCFP have anti-hepatic fibrosis effects,and the mechanism may be closely related to reducing the deposition of interstitial collagen,improving the antioxidant capacity of the liver and regulating the expression of TGF-1/Smad signaling pathway-related proteins.