Abstract Diabetes affects the heart muscle, causing both systolic and diastolic heart failure; both insulin deficiency and insulin resistance promote dyslipidemia. Effect of aqueous extract of Calotropis procera leaf was evaluated on lipid profile and atherogenic markers in alloxan-induced diabetic rat using standard procedures. Adult albino rats (Wistar strain) of mean weight 100.0±2.0g were randomised into six groups (A-F) such that group A (non-diabetic) orally received 0.5ml of distilled water once daily for 10 days. Animals in group B, C, D, E and F which were made diabetic with alloxan (150 mg/kg body weight i.p) also received once daily 0.5ml of metformin (2.5 mg/kg b.w p.o), 25, 50 and 100 mg/kg body weight o.p. of the extract respectively. The results revealed that blood glucose of the alloxanised rats significantly and progressively reduced in the metformin – and extract – treated animals within 36 hours. Total cholesterol, LDL-c, triacylglycerol, Log (TG/HDL-c), observed in distilled water-treated diabetic rats were significantly reduced (p<0.05) in the extract – and metformin – treated rats. The reduction in HDL-c and TG/LDL-c in the distilled water-treated diabetic rats was also reverted back to the range of the non-diabetic controls by the extract and metformin. The significant reduction (p<0.05) in the elevated blood glucose level and correction of altered lipid profile observed in aqueous extract treated diabetic animals by Calotropis procera leaf to the range of non-diabetic controls in this study indicate the anti-hyperglycemic and anti-hyperlipidemic activity of the extract. In conclusion, Calotropis procera leaf can serve as a potent agent for the prevention of coronary heart diseases through its anti-hyperlipidemic property. Further study is recommended for the identification of the bioactive compounds in Calotropis procera leaf that exert the anti-hyperlipidemic property offered by the plant.