Currently, search of new plant compounds possessing anticancer and antioxidant activity is a vital area of research in plant medicine, as plant products are safe and relatively low of cost. Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for many diseases in India. In recent times, berberine has been revealed to have potent anticancer activity against various cancers. Information regarding the effect of berberine on experimental lung cancer is limited. The objective of the present study to evaluate the antioxidant potential of berberine on experimental lung carcinogenesis. Thirty Swiss albino mice were divided into five groups of six animals each. Animals in group I received corn oil orally and served as control. Group II were administered with 50 mg/kg b.wt. of benzo(a)pyrene (B(a)P) twice a week for 4 consecutive weeks to induce lung cancer by the end of 16th week. Group III received 50 mg/kg b.wt. berberine on alternate days for 16 weeks immediately after the first dose of carcinogen. Group IV also received berberine as in group III but from the sixth week of B(a)P induction till the end of the experiment. Group V animals constituted the drug control and received berberine alone. The results showed that berberine treatment remarkably down regulated lipid peroxidation and unusually improved the antioxidant defense. The reason for this noteworthy restoration might be due to the effect of the interference approach on the down regulation of the peroxidation reaction through the potent antioxidant nature, which ultimately reflected in the down regulation of lipid peroxidation. The histopathological study of lung tissues also confirms the biochemical changes. It can be concluded that berberine shows evidence of anticarcinogenic activity by reducing peroxidation reaction through enhancing antioxidant defense. The results justify the therapeutic applications of the active compound in the indigenous system of medicine, augmenting its therapeutic value.