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Purpose: We sought to determine whether obesity prevention by exercise conferred protection against subsequent ischemia-reperfusion injury (IRI) to the fatty liver of the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat after temporary vascular occlusion of 70% of the liver. Methods: At 19 week of age, male OLETF rats (n= 7-8/group) were randomized to groups of sedentary (OLETF-SED)-IR, running exercise (OLETF-EX)-IR, or OLETF-SED-nonIR. Nonhyperphagic, control strain Long-Evans Tokushima Otsuka (LETO) rats were similarly assigned. Rats in the running exercise groups were subjected to running training on a motorized treadmill for 5 weeks. The rats anesthetized with pentobarbitone were cannulated in the carotid artery and jugular vein. After laparotomy, the bile duct was cannuated for measurement of bile flow rate. A laser Doppler probe was placed on the left lateral lobe to monitor peripheral liver blood flow (LBF). Regional ischemia was induced by applying an atraumatic vascular clip around the entire vascular supply to the median and left lateral lobes, enabling vascular occlusion of 70% of the liver, for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine transferase (ALT) estimation (as a measure of parenchymal injury) were drawn immediately prior to ischemia, as well as 60 and 120 minutes after reperfusion. LBF and bile flow rate were measured at 15 min intervals. Results: Exercise attenuated the increases in body weight and liver weight in the OLETF-SED rats. The ALT levels after reperfusion in the OLETF-SED rats were greater than that in the OLETF-EX rats as well as the LETO-SED rats. Exercise attenuated the reduction in LBF and bile flow rate due to ischemia-reperfusion in the LETO-SED group. In contrast, exercise did not provide significant influences on the LETO-SED rats. Conclusion: Exercise attenuated the obesity and the ischemia reperfusion-induced disturbances of hepatic microcirculation and parenchymal injury of the hyperphagic, Otsuka Long-Evans Tokushima Fatty rats. [ABSTRACT FROM AUTHOR]