Microcirculatory derangement, energy depletion and lipid peroxidation have been related to development of ischemia-reperfusion injury in the liver. This study investigates the effects of hyperbaric oxygen (HBO) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Three groups were evaluated: 1) sham-operated control (laparotomy only, no ischemia, no HBO), n=8; 2) ischemia control (1-h ischemia, 2-h reperfusion, no HBO), n=8; and 3) HBO pretreatment (100% oxygen, 2.5 atm absolute, 90 min) plus ischemia (1-h ischemia, 2-h reperfusion), n=8. An in vivo microscope was used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) were determined. In comparison with the ischemia control group, HBO significantly improved harmful insults following ischemia-reperfusion. HBO lessened adherent leukocyte count (6.00±1.31 cells/200 µm vs 11.38±2.88 cells/200 µm), and improved flow velocity (1.72±0.26 mm/s vs 0.83±0.19 mm/s) in post-sinusoidal venules. HBO also reduced MDA (1.04±0.24 nmol/mg protein vs 2.24±0.49 µmol/g protein), and increased ATP(2.03±0.17 µmol/g wet wt vs 0.73±0.11 µmol/g wet wt) levels. This study demonstrates that HBO before ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model.