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Objective: Exposure to the phosgene can result in acute lung injury(ALI).Melatonin(MT),a hormone released from the pineal gland,has suggested to involve in multiple biological process.However,its role in phosgene induced ALI hasnt been explored yet.The aim of this study was to assess the therapeutic role of melatonin in phosgene induced ALI and explored the related mechanisms.Materials and methods A rat model of phosgene induced ALI was established and the severity of the ALI was evaluated by wet/dry (W:D) ratio of lung weight,bronchoalveolar lavage (BAL) fluid cell counts and inflammatory cytokines.Then MT,ulinastatin(UTI),p38 inhibitor and NF-κB inhibitor pyrrolidine dithiocarbamate(PDTC) were used alone or combined to treat the ALI and improvement of the ALI was assessed.The mechanism of melatonin was explored via evaluating Wnt/β-catenin pathway.Results After establishment of the rat phosgene induced ALI model,we found that MT alone or MT with UTI can significant improve the severity of the ALI and we also found that expression upregulation of Wnt and β-catenin might involve in improvement effect.Conclusions MT might be used as a therapeutic adjuvant in phosgene induced ALI.The combination of MT and UTI can serve as a better choice in phosgene ALI treatment.Expression upregulation of Wnt and β-catenin might involve in improvement effect of MT and UTI.