ABSTRACT The present study was designed to evaluate the cardioprotective effect of cranberry extract (75 and 150mg/kg.b.w.) against nicotine-induced heart toxicity in rats. Oral administration of nicotine (2.5mg/kg.b.w.) led to significant increase in plasma and heart transaminases (L-alanine and L-aspartate), lactate dehydrogenase (LDH), creatine Kinase (CK), and TBARS as well as plasma total- and direct bilirubin, triglyceride, total cholesterol, and LDL-cholesterol. Also, treatment of rats with nicotine led to significant decrease in plasma and heart GSH, superoxide dismutase (SOD), catalase (CAT) as well as plasma HDL. The obtained results revealed that cranberry extract (75 and 150mg/kg.b.w.) prevent heart tissue damage through increasing of GSH, SOD and CAT activities and decrease significantly TBARs level. These results suggest that, cranberry may be effective in enhances the protection of heart toxicity by its radical scavenging effect and antioxidant activity.