Objective:To investigate the protective effects of Lactobacillus casei Zhang ( Lcz) on mice with Acetaminophen (APAP)-induced acute liver injury.Methods:Mice were randomly divided into five groups:Control group (ctrl),APAP-induced liver injury group ( APAP ) , N-Acetylcysteine positive control group ( NAC ) , Lcz preventive group ( Lcz/APAP ) and Lcz control group (Lcz).Mice were orally administrated with Lcz (1×109 CFU/ml) for 30 continuous days prior to APAP exposure.Positive control group were intraperitoneally injected with 150 mg/kg NAC 1 h before APAP challenge.Mice in the APAP,NAC and Lcz/APAP group were intraperitoneally injected with 300 mg/kg APAP.Blood and liver samples were collected 18 h post APAP challenge.The expression of HO-1,SOD2,Bcl-2 and TLR4 were detected by Western blot.Results: Lcz could significantly inhibit APAP-induced increase in ALT and AST levels.Furthermore,pretreatment with Lcz increased the hepatic expression of HO-1,SOD2 and Bcl-2,while suppressing the expression of Toll-like receptor 4 (TLR4).Conclusion:Lcz can protect against APAP-induced acute liver injury in mice.The hepato-protective effects of Lcz are associated with its anti-oxidative and anti-inflammatory capacity.