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Background: Doxorubicin (DOX) is an anthracycline antineoplastic which causes hepatotoxicity by induction of free radicals and inflammatory liver tissues. Quercetin (QCT) is considered as a potent antioxidant that may ameliorates hepatotoxicity. Aim of the work: The current study was designed to detect the toxic effects of DOX in liver cells and evaluating the possible protective role of QCT against those toxic alterations in adult male albino rats. Materials and methods: forty (40) male albino rates were divided to four groups: Control (group I), DOX-treated (group II): Rats received 18 mg/kg of body weight of DOX. Group III, received 60 ml/kg of QCT combined with DOX. Group IV treated with DOX plus 100 ml of QCT/kg. After scarification of rats, liver enzymes and the bile levels were estimated. The livers were extracted and used in oxidative stress markers, histological and immunological studies. Results: Doxorubicin administration induced an increase in liver enzymes, bile level and oxidative stress markers. QCT administration induced an improvement in those levels, especially with the high dose. The microscopic examinations of the DOX-treated sections showed loss of normal architectures of hepatic cells, enlargement and congestion of the central and portal veins and blood sinusoids, vacuolar degeneration, cholelithiasis and necrosis of H&E stained hepatocytes. PAS-stained liver sections in the DOX-treated group showed an increase in the depth of the stain. Quercetin administration improved these changes and hepatocytes which stained with PAS showed moderate to mild staining, especially with the high dose of QCT. Sections of the stained liver caspase-3, in DOX-treated group showed positive results with intensity. QCT treated groups showed little effects of caspase-3, especially with the high dose. Conclusion: Doxorubicin had toxic effects on rats' livers, with significant improvement after treatment with QCT as an antioxidant substance, and its high doses were more protective than low doses.