A popular diet used for weight reduction is the low carbohydrate diet, which has most calories derived from fat and protein, but effects of this dietary regimen on coronary vascular function have not been identified. We tested the hypothesis that obesity-induced impairment in coronary endothelial function is reversed by a low carbohydrate diet. We used 4 groups of male Zucker rats: lean and obese on normal and low carbohydrate diets. Rats were fed ad libitum for 3 weeks; total caloric intake and weight gain were similar in both diets. To assess endothelial and vascular function, coronary arterioles were cannulated and pressurized for diameter measurements during administration of acetylcholine, sodium nitroprusside, or during flow. Compared to lean rats, endothelium-dependent acetylcholine-induced vasodilation was impaired by about 50% in obese rats (normal diet), but restored to normal by the low carbohydrate diet. When fed the normal diet flow-induced dilation (FID) was impaired by over 50% in obese compared to lean rats. Similar to acetylcholine, responses to FID were restored to normal by a low carbohydrate diet. L-NAME (10 µM), an inhibitor of NO synthase, inhibited acetylcholine- and flow-induced dilation in lean rats, but it had no effect on acetylcholine- or flow-induced vasodilation in obese rats on a low carbohydrate diet. TEA a non-specific K channel antagonist blocked flow-dependent dilation in the obese rats, suggesting that the improvement in function was mediated by a hyperpolarizing factor independent of NO. In conclusion, obesity-induced impairment in endothelial dependent vasodilation of coronary arterioles can be dramatically improved with a low carbohydrate diet most like through the production of a hyperpolarizing factor independent of NO.