Introduction: The anti-epileptic medication Valproic acid (VPA) can damagedamage DNA and interfere with the mitochondria’s capacity to metabolize energy. Consequently, VPA is a strong teratogen for the progeny of expectant mothers. OM3FA’s capacity to preserve the cell membrane integrity of neural tissues improves cognitive function and Alzheimer’s disease. Aim of work: To determine postnatal neuroprotective impact of Omega-3 on cerebral cortex in Valproic acidtreated rat model. Material and methods: Forty adult pregnant female albino rats were randomized into 4 groups equally: the control negative group (group I) which didn’t receive any medications, the Omega3 treated group (group II) which received Omega3 (144 mg/Kg/ day) orally once daily and the Valproic Acid treated group (group III) which received Valproic Acid oral solution (50 mg/Kg/day) once daily using gastric tubes and the Valproic Acid +Omega3 treated group received VPA(50 mg/Kg/day) and Omega3(144 mg/Kg/ day) once daily. Then the cerebral cortex of all offspring were processed at 7th and 21th day after birth to be evaluated biochemically, histologically, immunohistochemically, and morphometrically. Results: Histologically and immunohistochemically, the group treated with Valproic Acid revealed remarkable degenerative and neuronal apoptotic changes of the cerebral cortex six layers. The group treated with Valproic Acid+Omega3 showed enhancement in the histological, and immunohistochemical alterations. As regards the biochemical (MDA &TAC) and morphometric results Valproic Acid+Omega3 showed statistically significant improvement in comparison with the Valproic Acid. Conclusion: Valproic acid consumption during pregnancy documented to have neurotoxic impact on cerebral cortex structure of the rat offspring. Omega3 has a protective effect against Valproic acid neurotoxicity.