Polymethoxyflavones (PMFs) in citrus have been of increasing interest due to its extensive biological activities. Nobiletin (NOB),one of the main substances of PMFs,has been reported to exhibit anti-oxidant,anti-inflammatory,anti-cancer,and nerve protection resistance activities. Although the anti-inflammatory activity of PMFs has been already reported,its involvement in lung protection has rarely been reported. This article is aimed to investigate the protective effects of PMFs in Citrus reticulata‘Chachi’ on acute lung injury (ALI) induced by lipopolysaccharide in mice. PMFs were extracted from Citrus reticulata‘Chachi’ and purified. The structure of PMFs in citrus was identified. A mouse model of acute lung injury was established by intranasal instillation of lipopolysaccharide. The effects of PMFs on ALI were explored by measuring the degree of lung tissue damage,the wet/dry mass ratio of lung tissue,the activity of oxidative damage indicators,and the content of pro-inflammatory cytokines. The results showed that the main components of the extracted PMFs were the nobiletin and tangeretin (About 80% in the PMFs). PMFs with the contents of 250 mg/kg and NOB with the contents of 50 mg/kg significantly alleviated ALI. It is indicated that PMFs and NOB have good anti-oxidant and anti-inflammatory effects,and have a certain protective effect on ALI.