〔Abstract〕 Objective To explore the mechanism of rosiglitazone(RSG) pretreatment in reducing inflammation and oxidative stress in the procession of acute lung injury(ALI) induced by bacterial lipopolysaccharide(LPS) in mice. Methods 32 SPF CD-1 male mice were randomly divided into Control group, RSG group, LPS 6 h group and RSG+LPS 6 h group. Mice in LPS group and RSG+LPS 6 h group were injected intraperitoneally with a single dose of LPS(2 mg/kg), while mice in RSG+LPS 6 h group and RSG group were given RSG(10 mg/kg) by oral gavage once a day for 4 days before LPS injection. The mice were killed 6 h after LPS injection, and the serum and lung tissue were collected. The pathological changes of lung tissue were evaluated by HE staining and pathological score, the levels of serum inflammation chemokine Keratinocyte-Derived Chemokine(KC) and proinflammatory factor Tumor Necrosis Factor-α(TNF-α) were detected by ELISA method, the protein expressions of NADPH oxidase subunits NOX-2,NOX-4 and nuclear factor-kappa B(NF-κB) signaling pathways(IκBα,p-IκBα,p-p65) in lung tissue were measured with Western blotting method. Results RSG pretreatment significantly attenuated LPS-induced ALI. RSG pretreatment obviously reduced the elevation of LPS-induced KC and TNF-α in lung tissue of mice, and the activation of LPS-induced NF-κB signaling pathway in lung tissue of mice was remarkedly alleviated. RSG pretreatment markedly inhibited the increase of NOX-4 protein in mice lung tissue induced by LPS. Conclusion RSG pretreatment may attenuate LPS-induced ALI in mice by inhibiting pulmonary inflammation and oxidative stress.