Hyperpermeability is a crux of pathogenesis of sudden lung edema in many pulmonary disorders. especially in acute lung injury and adult respiratory distress syndrome（ARDS）. Using our modified method for assessment of pulmonary vascular permeability. we observed the effects of xanthine with xanthine oxidase（X-XO） perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide（VIP） against the injury of pulmonary vascular permeabilrty. After addition of xanthine oxidase in the perfusate reservoir containing xanthine￣（125） I-albumin leak index （￣（125）IALI）was remarkably increased while peak airway pressure（Paw） was not significantly increased

and perfusion pressure of pulmonary artery（Ppa）and lung wet/dry weight ratio（W/D） were only slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B

2

（TX B

2

） and 6-keto-prostaglandin F

1α

(6-keto -PGF

1α

) in the perfusate. Treatment with VIP obviously reduced or totally prevented all signs of injury. Simultaneously

VIP also diminished or abolished the associated generation of arachidonate products. The results indicated that VIP has potent protective activity against injury of pulmonary vascular permeability and may be a physiological modulator of inflammatory damage to vascular endothelium associated with toxic oxygen metacolites.