Background: Iron overload and its accumulation in the heart is a frequently encountered condition, especially in association with certain hematologic conditions such as inherted hemoglobinopathies, i.e thalassemia. This myocardial iron overload may be associated with a decrease in the antioxidant Vit. E and may catalyze oxidant damage to mitochondrial DNA leading to cardiac dysfunction, failure and even death. Objective: The aim of this study was to determine and explain the possible mechanisms of the effects of chronic iron overloading (CIO) on cardiovascular function in a rat model together with determination of the possibility of using vitamin E supplementation as a potential protective target. Materials and methods: Thirty healthy adult male albino rats of initial body weight 220-250 gm were included. Rats were randomly and equally divided into 3 groups: Group (1): Vehicle-treated (control) group, group (II): Iron overload group, and group (III): iron overload group treated with vitamin E. Rats were examined for the serum iron, ferritin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), cardiac troponin I (CTnI), malondialdhyde (MDA), catalase activity (CAT), superoxide dismutase (SOD) activity, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin (APN) levels. Heart rate, blood pressure, duration of P wave, P-R, R-R and QTc intervals of ECG, and histopathological examination for the heart and aorta were also evaluated. Results: The present study revealed that chronic iron overloading significantly increased serum LDH, CPK, CTnI, MDA, IL-6 & (TNF-α) levels with a significant positive correlation with serum ferritin level, but significantly decreased serum CAT activity, SOD activity, and APN levels with a significant negative correlation with serum ferritin level and also decreased heart rate and blood pressure together with prolongation of duration of P wave, P-R, R-R & QTc intervals of ECG. Also, iron deposition in the cardiac and aortic tissues with deterioration of their histoarchitecture has been shown. Moreover, it was found that exogenous administration of vitamin E resulted in a significant recovery of all the above-mentioned parameters in the iron overloading group. Conclusion: The present study demonstated that CIO is associated with deposition of ion in cardiovascular system (CVS) leading to its dysfunction which is termed secondary cardiomyopathy. This dysfunction could be attributed to oxidative stress, inflammation and/or reduced adiponectin levels .Vitamin E as an antioxidant has a protective effect that can strongly ameliorate this dysfunction.