Abstract: Objective To study an appropriate murine model for this research, the mice were administrated by gastrogavage with CCl4, D-GalN/LPS, D-GalN/TNF-α and ConA to induce acute liver injury in different group, respectively. Methods The 80 mice were randomly separated from 152 male mice (6-8 weeks). The 80 mice were randomly divided into CCl4 ＋ H2O group, CCl4 ＋ Sedum Sarmentosum (SS) group, D-GalN/LPS ＋ H2O group, D-GalN/LPS ＋ SS group, D-GalN/TNF-α ＋ H2O group, D-GalN/TNF-α ＋ SS group, ConA ＋ H2O group, and ConA ＋ SS group (10 mice per group) with the injection of CCl4, D-GalN/LPS, D-GalN/TNF-α and ConA in different groups, and all the mice were administraged by gastrogavage with SS at same time. The survival rate were observed. The 72 mice were randomly divided into Normal group, CCl4 ＋ H2O group, CCl4 ＋ Sedum Sarmentosum (SS) group, D-GalN/LPS ＋ H2O group, D-GalN/LPS ＋ SS group, D-GalN/TNF-α ＋ H2O group, D-GalN/TNF-α ＋ SS group, ConA ＋ H2O group, and ConA ＋ SS group (8 mice per group). The mice were sacrificed and plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. Results The survival rate of CCl4 ＋ SS group mice was elevated from 55% to 90% (P = 0.0128). After 24 hours challenge, the serum ALT level was (5500.00 ± 426.20) U/L, AST (4383.00 ± 358.00) U/L and LDH (6764.00 ± 691.30) U/L of CCl4 ＋ SS group, lower than CCl4 ＋ H2O group ALT (10521.00 ± 1374.00) U/L, AST (7328.00 ± 947.80) U/L and LDH (13589.00 ± 1542.00) U/L (P ＜ 0.05). Conclusions Sedum Sarmentosum has an obvious protecting effect for acute liver injury induced by CCl4 in mice.