Background: As one of the most influential and in-demand nanoparticles for commercial applications, titanium dioxide nanoparticles (TiO2NPs) are commonly used in industry as a white pigment, in cosmetic and health products, and as a disinfection agent. In food and drugs, this additive is known as E171 and helps define colors clearly and can prevent UV degradation. This study used light and transmission electron microscopy to examine the effects of TiO2NPs on the liver in rats. Methods: Titanium dioxide nanoparticles were administered to 40 rats at 0, 10, 20, and 50 mg/kg of rat body weight suspended in one milliliter of distilled water over 60 days (every second day) by oral gavage. The rats were euthanized, and tissue samples were dissected from the liver for light (thick section) and transmission electron (thin section) microscopy study. Results: Histopathological examinations in treated groups revealed dilation of hepatic sinusoids, hepatocyte degeneration, and necrosis, observed as cellular swelling, cytoplasmic vacuolation, and loss of nuclei, nuclear pyknosis, karyorrhexis, and karyolysis. Some pathologic changes were also observed in mitochondria. All doses used in the study showed clear evidence of mitochondrial membrane and cristae enlargement, mitochondrial disintegration, and cristae destruction. Conclusion: Our study demonstrated that the continuous use of TiO2NPs (E171) can cause histopathological damage in the liver and disrupt the function of this organ. Consequently, it

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