Objectives: Both resveratrol (RV) and enriched environment (EE) exert beneficial effects on neurological functional recovery after an ischemic brain injury.Methods: The neuroprotective effect of combined treatment of RV and EE was examined in a rat model of middle cerebral artery occlusion (MCAO), aiming to further promote neurological functional recovery.Results: The combined therapy of RV and EE clearly improved locomotor activity and behaviour examination, compared to the monotherapy of RV or EE alone. Stroke severity was also markedly ameliorated by the co-treatment. Mechanistic study revealed that the combined treatment reduced oxidative stress. Moreover, the detrimental ERK1/2 signalling upregulated by MCAO injury was markedly suppressed by the co-treatment, compared to RV or EE monotherapy.Discussion: Altogether, the combined therapy of RV and EE showed a clearly enhanced neuroprotective effect, compared to RV or EE monotherapy, which might be a new strategy for the treatment of ischemic brain injury.