The present study aimed to evaluate cardio-protective effect of Nigella sativa oil (NSO) on lead induced cardio toxicity. Forty five albino adult rats were randomly divided into 3 groups: control lead (Pb) group that received lead acetate (20 mg/kg/day) 3 times weekly for 8 weeks and PB + NSO group (rats pretreated with Nigella sativa oil (4 ml/kg) orally for 1 h before administration of lead acetate (given as in Pb group). Myocardial injury was assessed by laboratory and pathological studies, and heart rate was recorded in all animals. Lead intake resulted in significant increases in cardiac high-sensitivity Creactive protein (hs-CRP), interlukin-6 (IL-6), E-selectin, troponin I, malondialdehyde (MDA) and serum creatine kinase-MB (CK-MB). The cardiac apelin, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) levels significantly decreased in Pb group compared to the control. Currently, heart rate and ST segment increased significantly after lead intake. Heart lesions as a result of lead treatment were in the form of hemorrhage, myocardial necrosis, mononuclear cell infiltration and fibrosis. Immuno histochemical results of the heart revealed positive cyclooxyenase-2 (Cox-2) expressions in Pb-treated group. NSO administration produced significant normalization of the physiological parameters as well as restored the histological structure and decreased the COX-2 expression of the heart compared to Pb group. In conclusion, NSO intake has cardio protective potential through its ability to decrease pro inflammatory cytokines, oxidative stress and cardiac tissue damage in lead-induced cardio toxicity.