Royal jelly (RJ) is known to have abundant nutritional properties and a variety of biological activities. To investigate the effects of RJ on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, were treated for 4 weeks with RJ (10, 30, and 300 mg/kg, p.o.). RJ treatment tended to decrease systolic blood pressure and significantly decreased serum levels of insulin and the Homeostasis Model Assessment ratio, an index of insulin resistance. In isolated and perfused mesenteric vascular beds of OLETF rats, RJ treatment resulted in significant reduction of the sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and potentiation of the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with that in untreated OLETF rats. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that RJ could be an effective and functional food to prevent the development of insulin resistance.