Titanium dioxide nanoparticles (TiO2 NPs) could affect biological targets like the brain. The aim of this study was to investigate the toxic effects of TiO2 NPs on the brain of adult male rats and to evaluate the protective role of N- Acetylcysteine (NAC) on the affected parameters. Sixty adult male Albino rats were divided into 4 groups; control group, NAC group: rats received NAC (100 mg/kg), TiO2 NPs group: rats received 1200 mg/kg TiO2NPs in 1ml of 5% gum acacia solution), TiO2NPs/ NAC groups rats received TiO2 NPs and NAC as previously mentioned. The rats were gavaged once daily for 12 weeks. After 6 and 12 weeks, rats were sacrificed and their brains were obtained for estimation of brain malondialdehyde (MDA), glutathione (GSH) levels and histopathological examination. The results revealed time dependent significant increase of MDA and decreased GSH levels. Histopathological examination showed vacuoles in the brain tissues, pyknotic nuclei, necrosis in the nerve cells and fibrosis of the nerve fibers. Bcl2 immunolocalization revealed time dependent weak reaction in the cytoplasm of nerve cells. These changes showed minimization after using NAC. The present results indicated that TiO2NPs induced time dependent oxidative stress and apoptosis in rat brain which could be ameliorated by co-administration of NAC