The use of nanoparticles has been progressively increasing. Titanium dioxide nanoparticles (Tio2NPs) are utilized in every daily life used products. Large-sized titanium dioxide (Tio2) has not been proven harmful in previous toxicity studies, whereas, because of their small size, nanoparticles can penetrate biological barriers reaching various body organs. This study aimed to detect the histological and immunohistochemical changes in the mice liver following exposure to Tio2NPs and the possible protective role of carnosine. Forty adult albino mice weighing 20-25 gm were equally divided into 4 groups: Group 1 (control group), received intraperitoneal injection of 2 ml normal saline (0.9% NaCl2) for 7 days; Group 2 (carnosine group), received carnosine orally at a daily dose of 200mg /kg by gavage for 7 days; Group 3 (Tio2 NPs group), received a daily dose of Tio2NPs (1944mg/kg) by intraperitoneal injection for 7 days; Group 4 (Tio2NPs+carnosine), received a daily dose of intraperitoneal injection of Tio2NPs (1944 mg/kg) and gavage of carnosine (200mg/kg) for 7 days. At the end of the experiment, all animals were sacrificed after being anaesthetized by ether inhalation. The liver was dissected and subjected to light microscopic histological examination and B cell lymphoma-2 (Bcl-2) immunohistochemical stain. In Tio2NPs treated mice, there were Tio2NPS engulfed by numerous Kupffer cells; dilated congested portal vein, central veins, and sinusoids; inflammatory cells infiltrations; hepatocytes with vacuolated cytoplasm and small darkly stained nuclei and necrotic foci. There was also an increase in area percentage of collagen, negative PAS reaction, and decrease in Bcl2 expression. Mice treated with Tio2NPs and carnosine showed mild hepatic destruction and less collagen deposition, positive PAS reaction and an increase in Bcl2 immunostaining. The results of this study support the use of carnosine as a protective agent against the hepatotoxic effects of Tio2NPs.