THE purpose of our study was to determine whether inhibiting the action of tumor necrosis factor-α (TNFα) attenuates brain injury and reduces inflammatory responses in the mouse during ischemia and reperfusion. Mice underwent middle cerebral artery occlusion (MCAO) for 1 h followed by 23 h reperfusion. Monoclonal neutralizing anti-murine TNFα antibody (mAb) was administrated intraventricularly in the mouse with temporary MCAO. Infarct volume in the anti-TNFα mAb treated mice was significantly smaller than that in the control group (p< 0.05). The number of intercellular adhesion molecule-1 (ICAM-1)-positive vessels in the ischemic area of the anti-TNFα mAb-treated group was significantly less than that in the control group. Our study demonstrated that blocking TNFα reduced brain injury and attenuated ICAM-1 expression during transient cerebral ischemia.