Abstract: 【Objective】 This study aimed to investigate the impact of the ethanolic extract of Forsythia leaves（FSLE） on acetaminophen（APAP）-induced liver injury and its underlying mechanism.【Method】 Forty-eight Kunming mice were randomly assigned to six groups: the blank control group（NC）,APAP liver injury model group（LD）,FSLE control group（FSLE）,and high,medium,and low doses of FSLE treatment groups（HFSLE+LD,MFSLE+LD,and LFSLE+LD）,with eight mice in each group. The liver injury model was established,and drug administration took place. The levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,superoxide dismutase（SOD） activity,glutathione（GSH）,malondialdehyde（MDA）,and hydrogen peroxide（H₂O₂） were assessed in each group of mice. Liver histopathological changes were observed through hematoxylin-eosin staining（HE）. TRAF2,NF-κB p65mRNA,and protein expression levels were measured,along with TNF-α,IL-1β,and IL-6 levels.【Result】 FSLE reduced ALT and AST activity,MDA,and H₂O₂ content,while increasing SOD activity and GSH content. It also ameliorated liver histopathology,decreased TRAF2 and NF-κB p65 mRNA and protein expression,and lowered TNF-α,IL-1β,and IL-6 levels in mice with liver injury.【Conclusion】 In conclusion,FSLE demonstrated hepatoprotective effects against APAP-induced liver injury by mitigating oxidative stress,modulating the TNF/NF-κB p65 signaling pathway,and suppressing the inflammatory response.