The present study was planned to investigate the effect of methomyl or imidacloprid on the brain of male rats. The effect grape seeds oil as an antioxidant was also evaluated. Animals were administered orally with 1/10 and 1/20 of LD₅₀ methomyl and imidacloprid with 17 and 450 mg /kg bw for four and eight weeks. Grape seeds oil with 4 ml/kg b.wt. was used for protection from methomyl and imidacloprid toxicity. Brain cortex and hippocampus oxidative stress (glutathione S transferase GST, glutathione peroxidase GPX, superoxide dismutase SOD, malondialdhyde MDA and nitric oxide NO), Na⁺,K⁺, ATPase and acetyl-cholinesterase AChE were determined. The result showed that GST, GPX, MDA, and NO₂ were increased significantly. But SOD, Na⁺K⁺ATPase and AChE were significantly reduced in comparison with the control. Grape seed oil induced a significant improvement for the pesticides brain toxicity but not to the level of control. The study suggested that the oil antioxidants not improve the brain toxicity induced by methomyl or imidacloprid.