Ｏｂｊｅｃｔｉｖｅ　The aim of this study is to explore the protective effect of edaravone（EDA） on lipopolysaccharides（LPS）-induced acute respiratory distress syndrome（ARDS） with pulmonary fibrosis in mice and their potential mechanism.　Methods　Seventy-two male ICR mice were divided into Sham group， LPS group and EDA group by completely randomized method. Each group was further divided into 1， 3， 7 d and 14 d group （n=6）. LPS（5 mg/kg） and equivalent saline was intratracheal instilled in LPS group and Sham group respectively. Intraperitoneal edaravone（5 mg/kg） was injected 1 h before and 12 h after intratracheal instillation of LPS in EDA group. At 1， 3， 7 d and 14 d， lungs were seized after animals were killed. Hematoxylin and eosin（HE） staining was used to observe of lung histopathology. Detection of lung wet/dry（W/D）， tumor necrosis factor-α （TNF?蛳α）， interleukin （IL）?蛳1β， malondialdehyde（MDA）， myeloperoxidase（MPO）， collagenⅠ（ColⅠ） and hydroxyproline（HYP） levels was performed. Immunohistochemistry was used to detect high mobility group box 1（HMGB1） in the lung tissue. The expression of HMGB1 and α?蛳smooth muscle contractile protein（α?蛳SMA） was detected by Western Blot.　Results　Compared with the same time point in Sham group， the lung tissue of LPS group showed significantly widened alveolar septa， a large number of inflammatory cell infiltration and partial alveolar collapse. Compared with the same time point in LPS group， the EDA group showed less inflammatory cell infiltration， interstitial lung exudates with significantly reduced damage of normal alveolar structure. Lung tissue W/D ratio， TNF-α， IL-1β， MDA content and MPO activity in LPS and EDA group was significantly elevated in 1 d， and then gradually decreased. EDA group TNF-α and IL-1β was significantly less than that in LPS group at the same time（P<0.05）. TNF-α and IL-1β levels in mice lung tissue of EDA group were significantly less than that in LPS group at the same time（P<0.05）. EDA-3， 7， 14 d group MDA levels of mice lung tissue was（6.94±1.07）， （5.31±0.95） nmol/mg prot and（3.16±0.37） nmol/mg prot， significantly lower than that in the LPS group［（9.15±0.30），（7.05±0.71） nmol/mg prot and（4.77±0.64） nmol/mg prot］ at the same time points（P<0.05）. EDA?蛳1， 3， 7 d group MPO lung tissue in mice were （0.051±0.007）， （0.040±0.008） U/g and （0.032±0.005） U/g， significantly lower than that in the LPS group［（0.066±0.011）， （0.050±0.014） U/g and （0.043±0.008） U/g ］ at the same time point（P<0.05）. The expression of HMGB1 increased in LPS-induced mice， mainly located in the cytoplasm. HMGB1 expression was significantly lower in the the EDA group than that in LPS group at the same time point（P<0.05）. Col Ⅰ， HYP levels of LPS group increased significantly in EDA group（P<0.05）. α-SMA expression in EDA-1， 3， 7 d group was significantly lower than that in LPS group at the same time（P<0.05）. ColⅠ， HYP content in mice lung tissue of EDA group was significantly lower（P<0.05）.　Conclusions　EDA plays the vital role of prevention of LPS-induced ARDS with pulmonary fibrosis by reducing the abnormal alveolar epithelial injury and repair to prevent progression of lung fibrosis due to inhibition of oxidative stress， abatement of inflammatory cytokines and slowing down or breaking the vicious cycle of inflammatory response.