Using the four-vessel extracranial one staged occlusion model of adult Wistar rats, we analyzed quantitatively released free fatty acids during ischemia. Also have we analyzed the effect of bifemelane to reduce free fatty acid accumulation after the onset of ischemia. Bifemelane (15 mg/kg, 30 mg/kg) and saline as control were intraperitoneally administered to adult Wistar rat prior to 30 minutes of experimentally induced ischemia. The results obtained were analyzed by one or two way analysis of variance (ANOVA). Physiological variables (systemic arterial pressure, PaO2, PaCO2, pH) did not change significantly in all four experimental groups. Total free fatty acid levels (sum of 5 fatty acid) increased significantly after ischemia (30 minutes). Higher dose (30 mg/kg) of bifemelane administration significantly reduced total free fatty acid accumulation, though lower dose (15 mg/kg) did have no effect. Bifemelane (30 mg/kg) reduced significant accumulation in the amount of saturated and monounsaturated fatty acid (palmitic acid [16:0], stearic acid [18:0] and oleic acid [18:1]). Arachidonic (20:4) and docosahexaenoic (22:6) acid failed to show any effective reduction by bifemelane pre-treatment of lower nor higher dose. Bifemelane is supposed to have many pharmacological effects such as increase in cerebral blood flow, augmentation of glucose uptake, monoamine metabolism, cerebral vasodilatation and platelet antiaggregation. Free fatty acid accumulation is effectively suppressed by the higher dose of bifemelane administration. Although the exact mechanism are not clearly identified by the result obtained in this experiment, selective inhibition of accumulation in saturated and monounsaturated fatty acids by bifemelane pretreatment may be obtained by the improvement of energy metabolism, which may help to reacylation of fatty acid into phospholipid.