Titanium dioxide nanoparticles are extensively used metal in cosmetics, sunscreens, food products, paints and drugs, producing oxidative stress and deoxyribonucleic acid damage. This study aimed to improve the overall (TiO2NP) use and decrease its related health hazards through the following objective among albino rates: To assess the TiO2NPs oral administration pulmonary induced toxic effect and to study the beneficial role of Idebenone as a novel agent protecting the human body against this toxic effect. An experimental trial conducted on 75 adult albino rats of both sex, rats were classified into; Group I, II: Negative, positive controls. Group III: Rats gavaged orally with 200 mg/kg b.w. Idebenone. Group IV: Rats received 250 mg/kg b.w. Titanium dioxide nanoparticles. Group V: Rats gavaged orally with Idebenone then Titanium dioxide nanoparticles with previous doses. The blood samples were withdrawn for estimating nitric oxide, reduced glutathione levels. Broncho-alveolar lavage fluid was collected for estimating oxidative stress markers and inflammatory cytokines (IL-6, TNF-α). Then histological examination and Comet assay from the lung tissues were done. The collected data were coded and analyzed using the suitable tests by the SPSS program. Titanium dioxide nanoparticles significantly decreased and increased in values of blood reduced glutathione and nitric oxide, respectively. In addition, it caused significant increase broncho-alveolar lavage fluid oxidative stress markers and inflammatory cytokines with marked histo-pathological changes in the lung cells were observed with DNA damage. Upon supplementation of Idebenone with titanium dioxide nanoparticles produced normalization of the oxidative stress markers and partial protection of pulmonary histological changes with moderate protective effects against DNA damage. Titanium dioxide nanoparticles exposure causes toxic effects on the lung and administration of Idebenone offers protection against its damaging effects.