Arterial baroreflexes may regulate resistance vessels supplying glucose to skeletal muscle by modulating efferent sympathetic nervous system activity. We hypothesized that selective manipulation of baroreflex activity through electrical carotid sinus stimulation influences insulin sensitivity by changing muscular glucose delivery. We enrolled 16 hypertensive patients who responded to treatment with an electrical carotid sinus stimulator. Patients were submitted to frequently sampled intravenous glucose tolerance testing (FSIGT) with the stimulator on and with the stimulator off on separate days in a randomized, double-blind, cross-over study. We monitored interstitial glucose, lactate, and pyruvate in the vastus lateralis muscle using microdialysis. Glucose and insulin concentrations in arterialized venous blood before and during FSIGT were virtually identical with the stimulator on and with the stimulator off. Insulin sensitivity, the primary endpoint of this study, was 3.3±1.0 (mU/L)(-1)*min(-1) and 4.4±2.6 (mU/L)(-1)*min(-1) (on vs. off; p=0.7). Interstitial glucose, lactate, and pyruvate increased similarly during FSIGT regardless of the stimulator settings. In conclusion, acute changes in baroreceptor stimulation did not elicit significant changes in muscular glucose delivery and whole body insulin sensitivity. Baroreflex-mediated changes in sympathetic vasomotor tone may have a limited acute effect on muscle glucose metabolism in patients with treatment-resistant hypertension (ClinicalTrials.gov NCT01355510).