Evidence implicating leukocytes as mediators of tissue injury in different disease processes is accumulating rapidly. The sequestration and activation of neutrophils have been shown to be key components in the pathophysiology of chronic inflammatory bowel diseases, and in gastrointestinal lesions following hemorrhagic shock, ischemia-reperfusion, and ingestion of nonsteroidal anti-inflammatory drugs, or ethanol. Leukocyte-endothelial cell interactions also appear to be a target for the action of various drugs proven to be useful in the treatment of gastrointestinal inflammatory disorders. This review focuses on the alterations in leukocyte-endothelial cell interactions in the aforementioned conditions.