Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsaturated fatty acid similar to one found in fish oil, yet less prone to peroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow, reflow reperfusion model were investigated in the rat. Rats were fed semisynthetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in both the control and treatment groups; average daily weight gain was around 4 g per 100 g rat weight in all three groups studied, and there were no significant differences in these parameters. Livers were initially perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fish oil treatment improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38 microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an indicator of the hepatic microcirculation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted increases in intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing juniper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improving the hepatic microcirculation in livers undergoing oxidant stress.