ObjectiveTo observe the therapeutic effect of Radix Paeoniae Rubra-Radix Aconiti Lateralis on acute-on-chronic liver failure （ACLF） rats and its effect on M1/M2 macrophage polarization. MethodMale SD rats were randomly divided into normal group， model group， positive group （lactulose， 1.8 g·kg^-1） and traditional Chinese medicine （TCM） group （Radix Paeoniae Rubra-Radix Aconiti Lateralis， 5.85 g·kg^-1）， six in each group. The ACLF rat model was established by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of D-galactosamine+lipopolysaccharide. Then the modeled rats were intervened with corresponding drugs for one week. The normal group and model group were given the same dose of distilled water. The histopathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expression levels of CD86， inducible nitric oxide synthase （iNOS）， CD206 and arginase 1 （Arg1） were detected by real-time polymerase chain reaction （Real-time PCR）， Western blot and immunohistochemistry. ResultCompared with the conditions in the normal group， pseudolobule formation in liver tissue and morphological changes and necrosis of hepatocytes were observed in ACLF rats， accompanied by a large number of inflammatory cell infiltration. Moreover， the mRNA and protein expression levels of CD86， iNOS were up-regulated（P<0.01）. Compared with the model group， the treatment groups had improved necrosis and inflammatory infiltration of hepatocytes， down-regulated mRNA and protein expression of CD86 and iNOS （P<0.01） and up-regulated mRNA and protein expression of CD206 and Arg1 （P<0.05， P<0.01）， with the up regulation in the TCM group better than that in the positive group. ConclusionACLF rats had unbalanced M1/M2 macrophage polarization， and the imbalance shifted towards M1. Radix Paeoniae Rubra-Radix Aconiti Lateralis inhibited the activation of M1 macrophages and reduced the inflammatory response of liver failure by promoting the polarization of liver macrophages towards M2.