Adenosine A receptors (AARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of AARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far. In this study, the expression of AARs after transient middle cerebral artery occlusion (MCAO) was evaluated by positron emission tomography (PET) with [F]CPFPX and immunohistochemistry (IHC). In addition, the role of AARs on stroke inflammation using pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with [F]DPA-714 (TSPO) and [F]FLT (cellular proliferation), as well as IHC and neurofunctional studies. In the ischemic territory, [F]CPFPX signal and IHC showed the overexpression of AARs in microglia and infiltrated leukocytes after cerebral ischemia. Ischemic rats treated with the AAR agonist ENBA showed a significant decrease in both [F]DPA-714 and [F]FLT signal intensities at day 7 after cerebral ischemia, a feature that was confirmed by IHC results. Besides, the activation of AARs promoted the reduction of the brain lesion, as measured with TW-MRI, and the improvement of neurological outcome including motor, sensory and reflex responses. These results show for the first time the PET imaging of AARs expression after cerebral ischemia in rats and the application of [F]FLT to evaluate glial proliferation in response to treatment. Notably, these data provide evidence for AARs playing a key role in the control of both the activation of resident glia and the proliferation of microglia and macrophages after experimental stroke in rats.