Objectives: To compare some of the cardioprotective effects of pretreatment with captopril and losartan on rat model of metabolic syndrome.Background: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) inhibit the renin-angiotensin system in different ways. The cardioprotective effect between captopril and losartan in normotensive patient was shown to be equal. However, the comparative effects in metabolic syndrome are still controversial.Methods: In the present study, 36 albino male rats (200 - 210 g) randomly assigned into six groups: normal non-treated group-I (receiving normal diet for 8week and 5ml/kg/d distilled water starting from 5th-8th wk); normal captopril-treated group-II (receiving normal diet for 8week and 50mg/kg/d captopril starting from 5th-8th wk); normal losartan-treated group-III (receiving normal diet for 8week and 20mg/kg/d losartan starting from 5th-8th wk); HFD non-treated group-IV (receiving high fructose diet for 8week and 5ml/kg/d distilled water starting from 5th-8th wk); HFD captopril-treated group-V (receiving high fructose diet for 8week and 50mg/kg/d captopril starting from 5th-8th wk); HFD losartan-treated group-VI (receiving high fructose diet for 8week and 20mg/kg/d losartan starting from 5th-8th wk). After 8 weeks the weight and blood pressure of each rat was measured. Rats in each group were subjected to 30 min of left anterior descending coronary artery occlusion followed by 2 hours of reperfusion with hemodynamic and electrocardiographic monitoring. Rats in each group had blood samples drawn for biochemical tests and aortic rings removed to study vascular reactivity and histomorphometrical study. The infarction size in heart of each rat was assist by TTC-stain. Results: Losartan in HFD losartan-treated group-VI caused significant reduction in mean blood pressure (100±18 mmHg), heart rate (259±15 beat/min), infarction size (21.4±5mm2) and insignificant de¬crease in aortic wall thickness (124±14μm), compared to HFD captopril-treated group-V that had mean arterial blood pressure (106±18 mmHg), heart rate (257± 40 beat/min) infarction size of (27.6±4 mm2) and aortic wall thickness of (145±24μm). cholesterol, uric acid were decrease and HDL was increased in losartan-treated groups III and VI received either normal diet or HFD compared to non-treated groups and captopril-treated groups that received matching diets. However, glucose, insulin, triglyceride, and angiotensinII were reduced in captopril-treated groups II and V received either normal diet or HFD compared to non-treated groups and losartan-treated groups that received matching diets. Captopril with HFD in group-V significantly decrease the vascular contractility of aortic ring to 8μg phenylephrin by 18 % (p<0.05) compared to losartan with HFD in group-VI. Both captopril and losartan caused decrease in heart rate and mean arterial blood pressure, aortic wall thickness, infarction size, glucose, insulin, cholesterol, triglycerides, uric acid angiotensinII CK and LDH, compared to HFD non-treated group-IVConclusions: Losartan decreased heart rate, mean arterial blood pressure, infarction size, vascular wall thickness, cholesterol and uric acid more than captopril in rat model of metabolic syndrome. However, glucose, insulin, triglyceride, and angiotensin II levels were improved by captopril compared to losartan in rat model of metabolic syndrome.