Monosodium glutamate (MSG) is widely used as food additive and flavor enhancer; however, consumption of high dose of MSG provokes oxidative stress in many organs and its safety and side effects on the body are still controversial. Therefore, it is crucial to investigate the long-lasting effects of MSG on cardiac muscle functions and structure. Forty male Wister albino rats were assigned into 3 groups. Control group was injected intraperitoneally with physiological saline for 7days. Second group was injected intraperitoneally with MSG at a dose of 4mg/g b.w/day for 7 consecutive days and then kept without any treatment till 45th day of the experiment. Third group was injected intraperitoneally with MSG at a dose of 6mg/g b.w/day for 7 consecutive days and then kept without any treatment till 45th day of the experiment. Monosodium glutamate significantly reduced body weight, force of cardiac muscle contractility, serum level of high-density lipoprotein, and superoxide dismutase activity in cardiac muscle, while it significantly elevated heart rate, serum levels of total cholesterol, low-density lipoprotein, triacylglycerides, atherogenic index and troponin T, activities of serum lactate dehydrogenase and creatine kinase-MB, malondialdehyde concentration, and P53 protein expression in cardiac muscle. In addition, it induced myocardial degeneration, cellular infiltration, deposition of collagen in cardiac muscle, and periodic acid-Schiff staining reaction. This study indicated that MSG exerted long-lasting functional and structural alterations in the heart of male albino rats through induction of oxidative stress, atherogenesis, and apoptosis.