Adiponectin exhibits pleiotropic effects, including anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective ones. Although some studies have documented brain expression in different rodent models of its receptors, AdipoR1 and AdipoR2, their global distribution remains incomplete. Here, we demonstrated that both AdipoR are widely distributed in the brains of adult mice. Furthermore, by double immunostaining studies, we showed that AdipoR1 and AdipoR2 are mainly expressed in neurons and blood vessels. Then, considering the wide distribution of both receptors and the neuroprotective effects of adiponectin, we tested the therapeutic effect of a single injection of the adiponectin receptor agonist, AdipoRON (5 mg.kg−1), 24 h after stroke in a model of middle cerebral artery occlusion technique (MCAO). Under our experimental conditions, we demonstrated that AdipoRON did not modulate the infarct volume, cell death, neuroinflammatory parameters including microglia activation and oxidative stress. This study suggests that a protocol based on multiple injections of AdipoRON at a higher dose after MCAO could be considered to promote the therapeutic properties of AdipoRON on the brain repair mechanism and recovery.