The objective of this study was to determine whether the effects of a fructose diet, which causes hyperinsulinemia, insulin resistance, and hypertension in male rats, are dependent on sex. Blood pressure was measured via the tail-cuff method, and oral glucose tolerance tests were performed to assess insulin sensitivity. Blood pressure in female rats did not differ between fructose-fed and control rats at any time point (126 ± 5 and 125 ± 3 mmHg at week 9 for fructose-fed and control rats, respectively) nor was there a difference in any metabolic parameter measured. Furthermore, the vascular insulin resistance that is present in male fructose-fed rats was not observed. After ovariectomy, fructose caused a significant change in systolic blood pressure from baseline compared with fructose-fed ovary-intact rats (change of 21 ± 5 vs. −2 ± 4 mmHg). The results demonstrate that females do not develop hypertension or hyperinsulinemia upon fructose feeding except after ovariectomy, suggesting that female sex hormones may confer protection against the effects of a fructose diet.