The prerogative potential of nobiletin, a polymethoxylated citrus flavone on the reduction of Chromium-induced oxidative stress-mediated hepatotoxicity in adult male rats was investigated. Chromium (Cr) is a toxic heavy metal element, which probably causes oxidative stress by impairing the hepatic antioxidant system. The present investigation is focused on (i) studying the toxic effect of chromium in the liver of rats, as well as (ii) the protective effect of nobiletin on chromium-intoxicated rats. Chromium (700ppm) was administered orally for 21 days at intervals of 24 h between subsequent treatments. Nobiletin (75mg) was pre-treated in both control and cadmium-treated rats. Animals were sacrificed on day 22 after the last treatment. The blood and liver tissues were collected and immediately immersed in PBS solution for the evaluation of biochemical variables, and a small lobe of the liver was fixed in 10% formalin for light microscopic evaluation. Following intoxication with chromium, a significant decrease was observed in the antioxidant system of the liver along with the increase in oxidative stress markers, which has been normalized by nobiletin pre-treatment.