Titanium dioxide (TiO 2 ) has many applications nowadays. Due to its extreme whiteness and brightness, it is widely used as a white pigment in a variety of materials such as food additives, toothpastes, medicines, paints and coatings. However there is lack of knowledge about human health impacts, due to their unique physical and chemical characteristics. The aim of this study was to assess the toxicity of TiO 2 nanoparticles on the brain, lung and liver in albino rats and its possible mediation by free radical damage. Thirty six adult female albino rats were used in this study. They were classified into three equal groups. Group I : negative control. Group II : positive control administered 1ml 5% gum acacia solution by oral gavage dialy. Group III : each rat was given Tio 2 nanoparticles by oral gavage in a daily dose 600 mg/kg body weight suspended in 1 ml 5% gum acacia solution. Six rats were sacrificed from each group after 60 and 90 days. The brain, lung and liver of all rats were removed and subjected to histopathological examination by light microscope and immunohistochemical staining for TNF-α. Also reduced glutathione (GSH) level in the blood and serum malondialdehyde (MDA) level were measured for all rats. The results revealed that TiO 2 induced significant pathological changes in the brain mainly filamentous neuron, pyknotic nuclei, congested blood vessels and edema. The lung showed significant pathological changes as thickened alveolar septa, emphysematous changes, cellular infiltrations, local lymphoid hyperplasia, and granulometus formation. The liver revealed hydropic degeneration, inflammatory cells infiltration, fatty degeneration and necrosis of hepatocytes. All histopathological changes were significantly increased depending on the duration of exposure. In addition, there was a duration-dependent increase in TNF-α. activation which is a marker for inflammation and apoptosis; in the brain, lung and liver of rats treated with Tio 2 . Blood GSH level was reduced and serum MDA level was increased in rats of TiO 2 group at different duration of the study compared to controls. It is concluded that TiO 2 NPs induced toxic effects on the brain; lung and liver which increase with increasing the duration of exposure, these effects may be mediated through inflammatory responses and oxidative damage. It is recommended that the use of TiO 2 especially as food additive and coloring agent must be judged and its environmental level should be continuously monitored. Abd El-Khalek et al ... H.; Xu, Y.; Cao, Z.; Zhou, T.; Xue, A.; Wang, Y.; Cen, X. and Zhao, Y. L. (2010) :´N MR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administra-tion´´. Nanotechnology, 21(12): 125105. Calafell, R.; Boada, J.; Santidrian, A. F.; Gil, J.; Roig, T.; Perales, J. C. and Bermudez, J, (2009) : ´´Fructose 1,6-bisphosphate reduced TNF-α-induced apoptosis in galactosamine sensitized rat hepatocytes through activation of nitric oxide and cGMP production´´. Euro J Pharmacol., 610:...