Objective: To investigate the effect of seabuckthorn berries extract(SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury(ALI) induced by lipopolysaccharide(LPS). Methods: Sixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone(Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha(TNF-α) and interleukin-6(IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factorkappa B(NF-κB) p65 in lung cells was determined by immunofiuorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase(IKK) and nuclear p65, as well as downstream proteins of E-selectin(CD62E) and intercellular adhesion molecule-1(ICAM-1), were determined using Western blot analysis. Results: Histopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fiuid(P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E(P<0.01). Conclusion: SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.