The objective of this study was to determine whether pulmonary endothelial expression of the adhesive glycoprotein P-selectin contributes to the lung injury and leukostasis observed after intestinal ischemia-reperfusion (I/R). The pulmonary capillary filtration coefficient and lung myeloperoxidase activity were determined in rat lungs isolated after 120 min of superior mesenteric artery occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase in the pulmonary capillary filtration coefficient compared with control and sham-operated rats. The increase in pulmonary microvascular permeability elicited by intestinal I/R was effectively prevented by pretreatment with a P-selectin monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The intestinal I/R-induced increase in pulmonary microvascular permeability was accompanied by a dramatic sequestration of granulocytes in the lung compared with control and sham-operated rats; however, neither the P-selectin nor the control MAbs affected this event. These results indicate that P-selectin contributes to the pulmonary microvascular dysfunction observed after intestinal I/R. The inhibition of intestinal I/R-induced lung injury by immunoneutralization of P-selectin appears to be unrelated to the accompanying lung leukosequestration.