Acute carbon monoxide (CO) poisoning causes neurotoxicity through induction of necrosis, apoptosis, lipid peroxidation and oxidative stress. Resveratrol (RES) is a natural polyphenolic phytoalexin that exhibits neuroprotective effects in ischemia/reperfusion due to its anti-apoptotic, anti-necrotic and strong anti-oxidant properties as well as its ability to activate pro-survival pathways. In this study, rats were exposed to CO 3000 ppm for 1 h. Immediately after poisoning and on the next four consecutive days, RES (1, 5 and 10 mg/kg) was administered intraperitoneally. On the fifth day, animals' brains were excised, and necrosis, lipid peroxidation level and the level of Akt, BAX and BCL2 expression were evaluated. The results showed that RES 10 mg/kg significantly reduced lipid peroxidation, but RES 1 and 5 mg/kg had no significant effect on this parameter. Furthermore, RES 5 and 10 mg/kg significantly increased Akt expression level, while BAX/BCL2 ratio was reduced by RES 1, 5 and 10 mg/kg. Moreover, RES reduced necrotic foci in the brain, but the best results were seen following treatment with RES 10 mg/kg. In summary, RES showed neuroprotective effect in CO-poisoned rats as it decreased necrosis and BAX/BCL2 ratio and increased Akt expression levels.