BACKGROUND: Blood-brain barrier(BBB) permeability and intravascular hydrostatic pressure are main factors for developing brain edema. Selective cooling of the brain could attenuate the ischemia-induced increase of BBB permeability. Because the method can provide driving pressure for edema formation, a beneficial effect of hypothermic perfusion on reducing edema would be questionable. The goal of this study was to evaluate the effect of isolated cerebral perfusion during the cerebral ischemia on the formation of brain edema. METHODS: Both vertebral arteries were cauterized, right carotid artery was cannulated to provide an infusion route. After left carotid artery was snared, cold saline was immediately perfused into the right carotid artery for 10 min in the perfusion group. To produce ischemia in no perfusion group carotid arteries were clamped bilaterally for 10 min. Brain water contents were measured using the kerosene/bromobenzene density gradient after reperfusion and compared with no perfusion and normal control group. RESULTS: Brain water content of perfusion group measured at 90 min after reperfusion showed increased water content compared to no perfusion and normal control group(p<0.05). However, at 180 min after reperfusion, there were no statistically significant differences between the perfusion and no perfusion group. CONCLUSIONS: Cerebral saline perfusion during the ischemia enhanced the formation of brain edema even though hypothermia could reduce BBB permeability. These results show driving force is more important than permeability for the development of brain edema in this type of experiments.