Objective To investigate the effect of Liensinine on lipopolysaccharide (LPS)?induced acute lung injury (ALI) in mice. Methods BALB/ c mice were randomly divided into six group: control group, LPS group, LPS + Liensinine (2 mg/ kg, 4 mg/ kg, 8 mg/ kg) groups, and dexamethasone group. Acute lung injury in mice was induced by nasal instillation of LPS. After 12 h, the pathological changes of lung tissue were observed. The levels of TNF?α, IL?6 and IL?1β in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The number of neutrophils in BALF was detected using Wright?Giemsa staining. Total protein content was detected by BCA protein quantification assay. The pulmonary capillary permeability was examined with Evans blue. The MPO activity, MDA content, SOD activity, and GSH content in lung homogenate supernatant were detected by spectrophotometry. The content of ROS in lung tissue was detected by flow cytometry. Results The LPS group showed inflammatory cell infiltration, thickening of bronchial alveolar wall and pulmonary congestion in the lung tissue, while Liensinine improved the lung injury. In the LPS group, the contents of TNF?α, IL?6 and IL?1β in BALF were significantly increased, the number of neutrophils and the content of total protein were significantly increased, pulmonary capillary permeability, MPO activity and MDA content were increased, SOD activity and GSH content were decreased, the content of ROS was increased; while the Liensinine group reduced the contents of TNF?α, IL?6, IL?1β in BALF, reduced the number of neutrophils and total protein content, decreased the pulmonary capillary permeability, attenuated MPO activity and MDA contents and increased SOD activity and GSH content, and reduced ROS content in the LPS?challenged lung tissue. Conclusions Liensinine protects mice from LPS?induced acute lung injury by its anti?inflammatory and anti?oxidative activities.