Individuals with hyperglycemia exhibit impaired exercise performance and functional vasodilatory response. Based on the importance of arachidonic acid (AA) metabolites in functional vasodilation and the increased thromboxane/prostacyclin ratio in diabetes, we hypothesized that chronic hyperglycemia in diabetes increases thromboxane receptor (TP)-mediated vasoconstriction, resulting in an attenuated functional vasodilation. Three groups of lean Zucker rats (8 wks old) were used to test the effects of chronic hyperglycemia on endothelial function: normal, streptozotocin (STZ, 70mg/kg ip) and STZ + Insulin (2U/day). After four wks of treatment, spinotrapezius arcade arterioles were chosen for microcirculatory observation. Arteriolar diameter was measured following muscle stimulation and 10 µM AA application in the absence and presence of 1 µM SQ29548 (SQ; TP antagonist). STZ rats exhibited significantly higher fasting glucose levels and attenuated functional and AA-induced dilation as compared to normal animals. SQ improved the vasodilatory responses in STZ rats with no effect in controls. Insulin treatment normalized both the glucose levels and the vasodilatory responses, and SQ treatment had no effect on functional or AA mediated vasodilation in STZ + insulin animals. These results suggest that the impaired functional vasodilation in diabetic rats is due to hyperglycemia mediated increases in TP-mediated vasoconstriction.