Background: Ischemic stroke is a major cause of death and disability worldwide. Despite decades of intense research, the beneficial treatment of stroke remains limited. Adiponectin, a circulating adipose- derived hormone, has beneficial actions on cardio- and cerebrovascular disorders. A low level of plasma adiponectin is associated with ischemic cerebrovascular disease. In the present study, the role of adiponectin in the pathogenesis of acute cerebral injury was investigated. Rats were divided into three groups: (i) Sham operated group; (ii) Ischemia/reperfusion (I/R) group, rats were subjected to one hour middle cerebral artery occlusion followed by 23 hours of reperfusion (I/R); (iii) Adiponectin-treated group, adiponectin (0.5 mg/kg) was injected through jugular vein 10 minutes after the onset of reperfusion. Adiponectin supplementation improved neurological function and resulted in reduction in infarction size, and brain edema, brain contents of malondialdehyde (MDA), brain levels of nitric oxide (NO) levels, tumor necrosis factor-alpha (TNF-α) and caspase-3. Moreover it enhanced SOD (superoxide dismutase). Results of the present study demonstrate that adiponectin exerts a potent cerebroprotective effect against I/R injury through its anti-inflammatory and anti-oxidant action and anti-apoptotic mechanisms. It might be a potential target for ischemic stroke therap