Background: The number of diabetics around the world will reach three hundred million by 2025. Vascular dysfunction is a common finding of both diabetes and glucose intolerance. The repercussions of hyperglycemia on the endothelium and smooth muscle cells contribute to the high risk of cardiovascular disease in type 1 and type 2 diabetes as well. Aim of the work: The purpose of this study was to investigate the possible immunomodulatory effect of vitamin E on the remodeling of aortic wall in STZ-induced diabetic rats histologically, immunohistochemically, and morphometrically. Materials & Methods: Thirty adult male albino rats were equally divided into 3 groups: control group, five rats received a single intraperitoneal injection of 0.1 ml.0.1 M citrate buffer (pH 4.4), and 5 rats administered 2 ml of corn oil by oral gavage; diabetes group injected intraperitoneally with 65 mg/kg of streptozotocin in 0.1 ml citrate buffer; diabetic+ vitamin E group given Vitamin E (300 mg/kg) for 10 weeks after induction of diabetes. Sections of aortic specimens were stained with H&E, Masson’s trichrome, and orcein and processed for immunological evaluation with anti-eNOS and anti-α-SMA. Results: Vitamin E mended the histomorphological changes induced by diabetes in the aortic wall. It significantly decreased tunica media thickness, collagen, and smooth muscle cells. Vitamin E also improved elastin destruction and enhanced the expression of eNOS in the endothelial cells and suppressed α-SMA immunoreactivity in the wall of the aorta in diabetic rats. Conclusion: Vitamin E ameliorated the histological remodeling of the aortic wall in diabetic rats that was confirmed histologically and immunohistochemically through the regulation of eNOS and α -SMA expression.