Intercellular adhesion molecule (ICAM)-1 has been previously implicated in the hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R). Although the effects of chronic ethanol (EtOH) consumption on the liver are well known, it remains unclear whether this condition renders the hepatic microcirculation more vulnerable to the deleterious effects of gut and/or hepatic I/R. The objectives of this study were to determine whether chronic EtOH consumption alters the severity of gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury, and to determine if ICAM-1 contributes to this response. Male Wistar rats, pair-fed for 6 weeks with either a liquid diet containing EtOH or an isocaloric control diet, were exposed to gut I/R. Intravital videomicroscopy was used to monitor leukocyte recruitment in the hepatic microcirculation, the number of nonperfused sinusoids (NPS), and plasma concentrations of endotoxin and tumor necrosis factor (TNF)-. Plasma ALT levels were measured 6 hr after the onset of reperfusion. In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS and plasma endotoxin, TNF- and ALT. In EtOH-fed rats, the gut I/R-induced increases in NPS and leukostasis were blunted in the midzonal region, while exaggerated leukostasis was noted in the pericentral region and terminal hepatic venules (THV). Chronic EtOH consumption also enhanced the gut I/R induced increase in plasma endotoxin and ALT. The exaggerated responses to gut I/R normally seen in EtOH-fed rats, were largely prevented by pretreatment with a blocking anti-ICAM-1 monoclonal antibody. In conclusion, these results suggest that chronic EtOH consumption enhances gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury in the pericentral region and THV via an enhanced hepatic expression of ICAM-1.