Introduction: Diabetes mellitus is accompanied with higher incidence of cardiovascular disorders. There is some evidence of antidiabetic and vascular function-improving potential of Amaranthus caudatus (AC). Endothelium-dependent effects of oral administration of AC for 8 weeks on contractile and relaxatory response of thoracic aorta from diabetic rats were investigated.Materials and Methods: Wistar rats were divided into control, AC-treated control, diabetic, ACtreated diabetic, and glibenclamide-treated diabetic groups. For induction of type 1 diabetes, streptozotocin at a dose of 60 mg/kg (i.p) was injected. Treated groups received AC-mixed pelleted food at a weight ratio of 6.25%. Body weight and serum glucose level was measured before the study and after 4 and 8 weeks. At the end of study, contractile reactivity of thoracic aortic rings to KCl and phenylephrine and relaxatory response to acetylcholine and sodium nitroprusside was determined using isolated tissue setup.Results: Serum glucose level significantly decreased in AS-treated diabetic group (P<0.05) versus untreated diabetics. In addition, endothelium-intact AC-treated diabetic group showed a significantly lower contraction to KCl and phenylephrine (P<0.01) as compared to diabetic group and endothelium removal abolished this response. Meanwhile, relaxation response of endothelium-intact rings to acetylcholine was significantly higher in AC-treated diabetic group as compared to diabetics (p<0.01). In addition, there were no significant changes amongst the groups regarding relaxatory response to sodium nitroprusside.Conclusion: Chronic oral administration of AC through affecting endothelial-related agents could decrease contractile response and enhance relaxatory response in aortic tissue of diabetic rat and this may be beneficial in prevention of long-term vascular complications of diabetes.