OBJECTIVE The selectins play an important role in the neutrophil-mediated injury after hemorrhagic shock and resuscitation. The aim of this study was to investigate the effect of P-selectin blockade after HS and resuscitation. METHODS Forty-eight Sprague-Dawley rats were subjected to controlled combined with uncontrolled HS and resuscitation. Rats were divided into three groups (n = 16/group): (1) sham, no HS; (2) control, HS + resuscitation + drug vehicle; (3) treated, HS + anti-P-selectin monoclonal antibody. Transaminase levels to measure hepatocellular injury, liver myeloperoxidase to assess neutrophil infiltration, and histology were analyzed and compared between groups. Survival was followed for 3 days and was compared statistically. RESULTS Survival significantly increased from 30% in the control group to 70% in the treated group. Hepatocellular and structural injury as well as neutrophil infiltration were significantly decreased in treated animals. CONCLUSIONS Blockade of P-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.