Objective To study the protective effect of β-aescin on lipopolysaccharide (LPS) induced-acute lung injury (LPS-ALI) and to explore the underlying mechanism. Methods Sixty male C57BL/6 mice were randomly divided into four groups including normal control group, β-aescin-treated group, LPS-ALI group, LPS-ALI combined with β-aescin-treated group, with 15 mice in each group. For LPS-ALI group, the mice were intraperitoneally injected with chloral hydrate and 10 mg/kg of LPS was then injected into the lungs through oropharyngeal intubation. For LPS-ALI combined with β-aescin-treated group, β-aescin(1 mg/kg) was intraperitoneally injected 0.5 hour before LPS injection. For normal control group or β-aescin control group, the same amount of PBS or β-aescin was intraperitoneally injected. Blood gas analysis of 1 mL blood taken from abdominal aorta was performed at 0.5, 2, 4, 6 and 8 hours after different treatments. Lungs were obtained at 3 days after different treatment for frozen sections preparation, HE staining, dry/wet mass (D/W) ratio, detection of MPO and MDA, and examination of TNF-α, IL-6 and IL-1β expression. Results β-aescin can significantly reduce the pathological changes of lung tissue, lower PaCO2 while increase PaO2 and D/W ratio, down-regulate the expression of TNF-α, IL-1β and IL-6 in LPS-ALI mice. Conclusion β-aescin can significantly reduce the degree of lung injury and improve function of gas exchange in LPS-ALI mice by inhibiting lipid peroxidation production and expression of pro-inflammatory factors.