Cardiovascular disease (CVD) is the leading cause of death in the United States, and is the major source of morbidity and mortality associated with diabetes mellitus. Because the incidence of diabetes continues to increase, reducing the risk of CVD in diabetes will continue to be a major focus of cardiovascular research. An early manifestation of diabetes-induced CVD is dysfunction of the vascular endothelium, as indicated by depressed production of NO. Our findings now demonstrate depressed activity of endothelial nitric oxide synthase (eNOS) in diabetes, and suggest that treating human coronary artery endothelial cells with allicin, the major bioactive organosulfur component in garlic extract, can restore NO production in these cells. Coronary artery endothelial cells (Lonza) were obtained from control (HCAEC) or diabetic (DHCAEC) donors, and NO production was measured by fluorescence microscopy via 4,5-diaminofluorescein diacetate. On average, NO production was depressed by 12.9% in DHCAEC compared to controls. Treating these cells for 20 minutes with 4 μM allicin restored NO production by 32.9%. Further, immunoblot studies revealed that diabetes decreased expression of eNOS protein by 20.3%; however, allicin was able to reverse this effect of diabetes. On average, eNOS expression was increased by 26% by overnight exposure to 5 μM allicin. Taken together, these data indicate that allicin improves endothelium-dependent NO production in diabetes by enhancing the expression and/or activity of eNOS in human coronary artery endothelial cells. These studies further suggest that this improved endothelial function likely contributes to the established health benefits of garlic consumption (e.g., lowering blood pressure), and also suggests a natural means of reducing the devastating consequences of diabetes on CVD. Future experiments are needed to identify the mechanism of allicin action on eNOS and in vascular endothelial cells.