Background: Acute respiratory distress syndrome is associated with a mortality of 45%. The authors investigated the possible mechanisms and effect of vascular endothelial growth factor on alveolar epithelial barrier permeability in acute respiratory distress syndrome mice model. Methods: Eighty Male BALB/c mice were randomly assigned to four group: PBS group, LPS group, sFlt group, or LPS+ sFlt group. The levels of vascular endothelial growth factor and total protein in bronchoalveolar lavage fluid were compared, together with lung injury score and the histopathology of alveolar epithelial barrier. The expressions of vascular endothelial growth factor and tight junction proteins mRNA in lung tissue were also studied. Results: Lipopolysaccharide (LPS) inhaling was accompanied with increasing lung vascular endothelial growth factor (VEGF) expression. Anti-VEGF with soluble fms-like tyrosine kinase-1 (sFlt-1) attenuated the lung injury effectively. Conclusions: Our data indicate that anti-vascular endothelial growth factor with soluble fms-like tyrosine kinase1 could maintain the normal structure and function of respiratory membrane in acute respiratory distress syndrome mice model and might be a suitable therapeutic tool for the treatment of acute respiratory distress syndrome.