To explore the protective effect of total flavonoid from Polygonum perfoliatum L.（TFP）on acute liver injury induced by carbon tetrachloride (CCl₄) in rats and explore its mechanism.The 70 female SD rats were randomly divided into 7 groups according to their body weight:normal group,TFP control group (200 mg/kg),CCl₄ model group,CCl₄+silymarin group (120 mg/kg) and CCl₄+TFP high,middle and low dose groups (200,100,50 mg/kg),with 10 rats in each group.The normal group and the CCl₄ model group were treated with distilled water (8 mL/kg),and the other groups were treated with corresponding doses of drugs once a day for 10 days.After the last administration,except the normal group and TFP control group,the other groups were intraperitoneally injected with 12% CCl₄ olive oil solution (5 mL/kg) to establish the model of acute liver injury.After fasting for 16 hours,the blood of the eyeball was taken and the liver tissue was collected.The liver function and oxidative stress in serum were detected by biochemical method,the level of inflammatory factors in liver tissue was detected by enzyme-linked immunosorbent assay (ELISA),the expression of SIRT6/NF-κB pathway related protein in liver tissue was detected by Western blot,the pathological changes of liver tissue were detected by HE staining,and the expression level of p-NF-κB p65 in liver tissue was observed by immunohistochemistry.The results showed that TFP could improve the index of liver function and the condition of liver injury,increase the ability of antioxidation and the expression level of SIRT6 protein,and decrease the expression of inflammatory factors and NF-κB and other related proteins in tissue.The results of this study suggest that TFP has a protective effect on CCl₄-induced acute liver injury in rats,and its mechanism may be related to the inflammatory response and antioxidation mediated by SIRT6/NF-κB pathway.