ABSTRACT The study was designed to evaluate the protective nature of the bioflavonoid hesperidin on nicotine-induced toxicity in male Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week for 22 weeks). The nicotine-treated rats showed a significant increase in the marker enzymes, cholesterol, triglycerides, phospholipids, and free fatty acids. There was a significant protection on hesperidin administration at a dose of 25 mg/kg body weight in nicotine-treated rats. This finding is supported by histopathological studies of liver, lung, and kidney. The results of the present study suggest that hesperidin showed protective effects against nicotine-induced toxicity.