Objective To investigate the mechanism of action of Qingre Jiedu Liangxue prescription in the treatment of mice with acute-on-chronic liver failure( ACLF). Methods A total of 36 male C57 BL/6 mice were randomly divided into normal group( n = 6),traditional Chinese medicine( TCM) group( n = 6),Western medicine group( n = 6),and model group( n = 18). All mice except those in the normal group were given intraperitoneal injection of 10% CCl4 three times a week for 8 weeks,and LPS 0. 5 mg/kg and D-gal 400 mg/kg were given after last injection. The mice in the model group were sacrificed at 3,12,and 24 hours after D-gal administration. After 4 weeks of intraperitoneal injection of 10% CCl4,the mice in the TCM group and the Western medicine group were given TCM or Western medicine by gavage for 4 weeks and were sacrificed at 3 hours after D-gal administration. Serum levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),and inflammatory factors were measured; HE staining and picrosirius red staining were used to observe liver pathological changes; immunofluorescence assay was used to observe F4/80 and CD11 b; immunohistochemistry was used to measure the expression of myeloperoxidase( MPO); Western blot was used to measure the expression of CD44,intercellular adhesion molecule-1( ICAM-1),and high-mobility group box 1( HMGB1). A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the SNK-q test was used for further comparison between two groups. Results Compared with the normal group,the 3-hour model group had significant increases in the serum levels of ALT and AST χ2= 51. 41 and 71. 22,( both P < 0. 001),and comparedwith the 3-hour model group,the TCM group had a significant increase in the serum level of interleukin-17 A( IL-17 A) and significant reductions in tumor necrosis factor-α( TNFα),granulocyte-macrophage colony-stimulating factor( GM-CSF),and interleukin-10( IL-10)( all P < 0. 01),as well as significant reductions in the expression of interleukin-1β( IL-1β),monocyte chemotactic protein 1( MCP-1),and interferon gamma( IFNγ)( all P < 0. 05). Compared with the model group,the Western medicine group had significant reductions in the serum levels of GM-CSF,IFNγ,and interferon beta( all P < 0. 05). HE staining showed that compared with the normal group,the model group had severe hepatocyte injury and significant inflammatory cell infiltration. Liver pathological changes were improved after the administration of TCM and Western medicine. The 3-hour model group had a significant increase in the expression of MPO compared with the normal group( P < 0. 05),and the expression of MPO gradually decreased in the 12-and 24-hour model groups( P<0. 05); the TCM group had a significant reduction in the expression of MPO compared with the 3-hour model group( P < 0. 05). The model group had significant increases in the expression of F4/80 and CD11 b compared with the normal group,and the TCM group had significant increases in the expression of F4/80 and CD11 b compared with the 3-hour model group. The model group had significant increases in the expression of CD44 and ICAM-1 compared with the normal group( both P < 0. 05),and the TCM and Western medicine groups had significant reductions in the expression of HMGB1,CD44,and ICAM-1 compared with the 3-hour model group( all P < 0. 05). Conclusion In mice with ACLF,Qingre Jiedu Liangxue prescription can reduce the serum levels of ALT and AST,improve liver injury,increase IL-17 A,and reduce TNFα,GM-CSF,IL-10,IL-1β,MCP-1,and IFNγ． In addition,Qingre Jiedu Liangxue prescription can reduce the expression of MPO,CD44,ICAM-1,and HMGB1 and increase the expression of F4/80 and CD11 b in liver tissue. It is suggested that Qingre Jiedu Liangxue prescription can improve liver injury by regulating neutrophils and Kupffer cells,and further studies are needed to investigate the specific mechanism.