BACKGROUND The effect of adrenomedullin, a vasodilatory peptide on transient middle cerebral artery (MCA) occlusion was investigated in rats. METHODS Transient MCA occlusion for 2 hours was made by using the intra-arterial suture method, followed by reperfusion. RESULTS An intravenous infusion of adrenomedullin (1 microg/kg/min) from one hour before ischemia to one hour after ischemia significantly reduced the infarct size and improved neurological deficits (p<0.05), without affecting systemic blood pressure or other physiological parameters. The infarct size was reduced with adrenomedullin by 25.4+/-12.7%, 31.3+/-5.8%, 31.6+/-6.1% respectively at the coronal level 6, 8 and 10 mm posterior from the frontal pole. Adrenomedullin also significantly inhibited the increase in myeloperoxidase (MPO) activity in the MCA area of the ischemic hemisphere after 22-hour reperfusion (control: 0.205+/-0.054 unit/g wet tissue, adrenomedullin group: 0.047+/-0.009 unit/g wet tissue, p<0.0001). CONCLUSIONS These data suggest that adrenomedullin reduces acute ischemic brain injury and one of is neuroprotective mechanisms may be derived from inhibition of the infiltration of neutrophils into the ischemic tissue.