Although the female sex is associated with renal protection in non-diabetic nephropathy, men and women with type 1 diabetes mellitus (T1D) have a similar risk of developing nephropathy. As hyperglycemia is associated with exaggerated effects on blood pressure and renal hyperfiltration in women versus men with T1D, we examined the influence of clamped hyperglycemia on flow mediated vasodilatation (FMD) to determine if this parameter contributes to sex-related differences in the vascular function. After a controlled diet for seven days, blood pressure, ultrasound derived FMD and circulating renin angiotensin system mediators were measured in men (n=30) and women (n=28) with T1D during clamped euglycemia and hyperglycemia. Men and women were similar in pre-study dietary parameters, age, diabetes duration, body mass index, HbA1c, renal function and proteinuria. The systolic blood pressure (SBP) was higher in men during clamped euglycemia (121±2 vs. 108±2 mm Hg, P<0.0001) and hyperglycemia (121±2 vs. 111±2 mm Hg, P<0.0001), as were the circulating levels of angiotensin II (P<0.05). SBP increased in response to hyperglycemia in women but not in men. Consistently with differences in blood pressure during clamped euglycemia, FMD was higher in women than in men (8.06±0.55 vs. 4.15±0.52%, P<0.0001). In contrast, between-group differences in FMD during clamped hyperglycemia did not reach significance owing to a decline in FMD in women, versus men, in response to clamped hyperglycemia (P=0.040 for between-group change in FMD). Clamped hyperglycemia suppresses FMD in women, but not in men, with uncomplicated T1D, which may contribute to the relative loss of protection against renal disease progression in women with T1D.