Background. Omega-3 (ω3) administration was shown to protect against hypoxic-ischemic injury. The objectives were to study the neuroprotective effects ofω3, in a model of global ischemia.Methods. Male Wistar rats were subjected to carotid occlusion (30 min), followed by reperfusion. The groups were SO, untreated ischemic and ischemic treated rats withω3 (5 and 10 mg/kg, 7 days). The SO and untreated ischemic animals were orally treated with 1% cremophor and, 1 h after the last administration, they were behaviorally tested and euthanized for neurochemical (DA, DOPAC, and NE determinations), histological (Fluoro jade staining), and immunohistochemical (TNF-alpha, COX-2 and iNOS) evaluations. The data were analyzed by ANOVA and Newman-Keuls as thepost hoctest.Results. Ischemia increased the locomotor activity and rearing behavior that were partly reversed byω3. Ischemia decreased striatal DA and DOPAC contents and increased NE contents, effects reversed byω3. This drug protected hippocampal neuron degeneration, as observed by Fluoro-Jade staining, and the increased immunostainings for TNF-alpha, COX-2, and iNOS were partly or totally blocked byω3.Conclusion. This study showed a neuroprotective effect ofω3, in great part due to its anti-inflammatory properties, stimulating translational studies focusing on its use in clinic for stroke managing.