In this study, the effects of fish oil treatment on hepatic reperfusion injury in a low-flow, reflow perfusion model were investigated. Rats were fed powdered diets containing either 5% corn oil or 5% encapsulated fish oil for 13 to 15 days. Average daily food intake in both control and fish oil groups was about 20 g per rat, and weight gain averaged 9 glratld. Livers were perfused at flow rates around 1 &g/min for 75 minutes, which caused cells in pericentral regions to become anoxic because of insufficient delivery of oxygen. When normal flow rates (about 4 mIJglmin) were restored for 40 minutes, reperfusion injury occurred. Upon reflow, lactate dehydrogenase (LDH) release increased from basal levels around 1 to 50 IU/g/h in livers from control rats, whereas fish oil treatment minimized values to 16 IUI g/h. Rates of bile production reached 23 pUg/h during reperfusion in livers from controls and 38 pIJglh in the fish oil-treated group. Oxygen uptake was about 110 pmoYg/h during the reperfusion period in livers from both groups. Malondialdehyde (MDA), an end product of lipid peroxidation, was released into the effluent perfusate at rates around 80 nmol/g/h during reperfusion in controls, and values were not affected by fish oil treatment. Portal pressure, an indicator of hepatic microcirculation, increased from basal levels of 3 to 10.5 cm HzO during reperfusion in controls, but was only elevated to 8.3 cm HzO in the fish oil-treated group. In addition, nyPan Blue distribution time, another indicator of hepatic microcirculation, was reduced significantly by 44% by fish oil treatment. It is concluded that fish oil minimized hepatic reperfusion injury, most likely by reducing the production of vasoconstrictive eicosanoids from arachidonic acid, thereby improving the hepatic microcirculation, which prevents cell death on reperfusion.