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The present study aims to investigate the protective effect of quercetin against Aroclor-1254–induced hepatotoxicity in rats. Male Wistar rats were grouped into Group I control received vehicle (corn oil; 1 mL/kg bwt); Group II quercetin alone (50 mg/kg bwt/day orally); Group III Aroclor-1254 (2 mg/kg bwt/day intraperitoneally); Group IV Aroclor-1254 + quercetin treated for 30 days. The Aroclor-1254 treatment caused significant alteration in the biochemical parameters (hydrogen peroxide, lipid peroxidation, reduced glutathione levels, and alkaline phosphatase activity). The expressions of apoptotic and antiapoptotic proteins and the liver histology of Aroclor-1254–exposed rats showed cytoplasmic degeneration along with infiltration of polymorphonuclear cells. Whereas simultaneous treatment with quercetin normalized all the biochemical parameters, consequently it inhibited apoptosis mediated by Aroclor-1254 by downregulating aryl hydrocarbon receptor, p53 and apoptotic protein (Bax, caspase-9, caspase-3) and upregulating the antiapoptotic protein (Bcl-2) expression patterns; thereby, quercetin reduces alteration in hepatocellular morphology. Thus quercetin exhibited hepatoprotective effect. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 26:522-532, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21466