〔Abstract〕 Objective To investigate the effects and mechanism of pretreatment with rosiglitazone(RSG) on lipopolysaccharide(LPS)-induced acute liver injury(ALI). Methods 42 male CD-1 mice were randomly divided into six groups(7 mice every group): Control group, RSG group, LPS 6 h group,LPS 12 h group,RSG+LPS 6 h group, RSG+LPS 12 h group. Mice were supplemented with RSG(10 mg/kg) by gavage five consecutive days before LPS solely injection in the RSG and RSG+LPS groups. All mice were singly intraperitoneal injected with LPS(2 mg/kg) in the LPS and LPS+RSG groups. In the Control group and RSG group, mice were intraperitoneal injected with equal normal saline. All mice were sacrificed at 6 h and 12 h after LPS injection. Mice livers were collected and weighted. Some livers were used for HE staining to observe inflammatory cells infiltration and pathological damage. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by Reitman. Serum tumor necrosis factor alaph(TNF-α) and macrophage inflammatory protein-2(MIP-2) were measuredviaELISA.The protein expression of activator protein 1(AP-1) signaling, NADPH oxidases(NOX) and antioxidant enzymes were detected using Western blot. Results RSG pretreatment alleviated LPS-induced inflammatory cells infiltration and pathological damage. RSG pretreatment inhibited LPS-induced upregulation of serum ALT and AST in mice. RSG pretreatment attenuated LPS-induced hepatic c-fos and c-jun phosphorylation. RSG pretreatment mitigated LPS-induced upregulation of hepatic NOX-4. RSG pretreatment attenuated LPS-induced upregulation of hepatic haem oxygenase 1. Conclusion RSG pretreatment prevents LPS-induced ALI partially through inhibiting hepatic AP-1 signaling and NOX, and regulating antioxidant enzyme.