Background: Recently Titanium dioxide nanoparticles (TNPs) are widely used in different fields as in medicinal and daily life purposes. Currently, high concerns have been directed to reveal TNPs toxicity in humans. A dietary carotenoid called lycopene, reported as a powerful antioxidant, is suggested to have a protective rule. The aim of this study: is to evaluate the reversibility of TNPs toxicity on the renal cortices of adult male albino rats and to clarify protective role of concomitantly administrated lycopene. Material and methods: Forty-eight adult male albino rats were divided equally into 4 groups;(I, control group) -Ia, rats received only regular diet and water for14 days and Ib, rats that were injected with 1 ml intra-peritoneal (IP) distilled water daily for14 days. (II group): received IP injection of TNPs (300 mg/kg) for14 days. (III group): received 10mg/kg daily lycopene for 7 days by gavage then IP injection of TNPs (300 mg/kg) daily for 14 days together with10mg/kg lycopene by gavage. (IV group): received IP injection of TNPs (300 mg/kg) daily for 14 days followed by another 14 days of balanced diet only without TNPs or lycopene. By the end of the experiment renal cortices specimens were processed for light microscopic, immunohistochemical and transmission electron microscopic (TEM) study. Results: Marked histopathological changes detected in II group were obviously avoided in the III group. While the IV group did not show significant statistical improvement. Conclusion: TNPs induce pathological ultrastructural changes in rat's renal cortex, that were ameliorated by co-administration of Lycopene.