Hypovitaminosis D has a negative impact on the cardiovascular system. We performed the current study to investigate the expression of Vitamin D Receptor (VDR) in atherosclerotic human male aortas and to examine the effect of different doses of Vit. D supplementation on VDR expression in the aortas of male rats fed a High-Fat Diet (HFD). Human participants included 50 atherosclerotic male patients with anterior myocardial infarction and 131 control healthy males. Fifty male Wistar rats were divided into 2 groups: Control (Cont.) group; n = 10 and HFD fed rats; n = 40. The latter was divided equally into 4 subgroups according to the dose of Vit. D supplemented. Vitamin D was supplemented in 3 doses: (0.025, 0.05, 0.075 µg/kg) for a duration of 17 weeks. VDR expression score was immunohistochemically evaluated in aortas of both human and animal study groups. The current study revealed that Vit. D levels were significantly lower in atherosclerotic patients with myocardial infarctions compared to the human control group. Concurrent administration of Vit. D suppresses the progress of atheromatous plaque in rats feed a HFD in a dose-dependent manner. Consequently, it could be concluded that Vit. D supplements are recommended as a prophylaxis in patients at high risk of coronary artery disease.