Objective To explore the mechanism of Yipi Yanggan Prescription in the treatment of precancerous lesion of liver in rats based on M1 type macrophage polarization-chronic inflammation-liver cell malignant transformation.Methods Totally 90 Wistar rats were randomly divided into blank group,model group,Hugan Tablet group and Yipi Yanggan Prescription high-,medium-and low-dosage groups,with 15 rats in each group.The blank group was injected distilled water intraperitoneally,and the other groups were injected 5 mL/kg of diethylnitrosamine intraperitoneally at 50 mg/kg per week(twice per week)for 16 weeks to induce the precancerous lesion of liver model.Starting from the second day of modeling,Yipi Yanggan Prescription high-,medium-and low-dosage groups were orally administered with 1.2,0.6 and 0.3 g/mL Yipi Yanggan Prescription,respectively.The Hugan Tablet group was orally administered with 921 mg/kg Hugan Tablet solution,the blank group and model group were orally administered with an equal amount of physiological saline for 16 consecutive weeks.The appearance of the liver was observed,ELISA was used to detect serum ALT,AST,ALP,AFU,as well as TNF-α,IL-6,iNOS and MCP-1 content,HE staining and Masson staining were used to observe the morphology of liver tissue,immunohistochemistry was used to detect the expressions of liver cell malignancy markers OV6,CK19,CD133 and EpCAM,qPCR was used to detect the mRNA expressions of CK19,CD133 and EpCAM in liver tissue,immunofluorescence co-localization was used to detect the co-expressions of M1 type macrophage markers CD68 with IL-6 and TNF-α.Results Compared with the blank group,the liver of the model group rats was hard,with a rough surface and dull edges,and a large number of nodules were visible,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 significantly increased(P<0.01),there were large areas of dysplasia nodules,inflammatory cell infiltration,and increased collagen fibers in liver tissue,the expressions of OV6,CK19,CD133 and EpCAM in liver tissue significantly increased,and the co-expressions of CD68 with IL-6 and TNF-α significantly increased(P<0.01).Compared with the model group,the number and size of liver nodules in each treatment group of rats decreased,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 were significantly decreased(P<0.01),hepatocellular dysplasia and inflammatory cell infiltration were significantly improved,collagen fibers decreased,and the expressions of OV6,CK19,CD133 and EpCAM in liver tissue were significantly decreased,the co-expressions of CD68 with IL-6 and TNF-α significantly decreased(P<0.05,P<0.01).Conclusion Yipi Yanggan Prescription may alleviate inflammation by inhibiting polarization of M1 type macrophages,improve liver cell malignancy,and exert therapeutic effects on rats with precancerous lesion of liver induced by diethylnitrosamine.