In patients with type 2 diabetes many factors contribute to increase morbidity and mortality by ischemic heart disease. One contributor may be the use of sulfonylurea drugs. Such a possibility, which first arose several years ago, has recently resurfaced after the discovery that sulfonylureas act by inhibiting KATP channels. In the heart, inhibition of these channels prevent ischemic preconditioning.The present study was designed to assess the effect of different types of the second generation sulfonylureas on warm-up phenomenon in diabetic patients with chronic stable angina. It included 40 patients with coronary artery disease (CAD), 10 of them were non-diabetic controls, 10 diabetic patients were chronically controlled on glibenclamide, 10 diabetic patients were chronically controlled on gliclazide and 10 diabetic patients were chronically controlled on glimepiride.This study concluded that the nondiabetic patient with chronic stable angina showed improvement in ischemic threshold when a second exercise test is performed 15 minutes after the first positive exercise test, due to ischemic preconditioning. The type 2 diabetic patients with chronic stable angina on therapeutic doses of glimepiride and gliclazide maintained this "warm up" phenomenon, while glibenclamide abolished it.