Epidemiological and clinical evidence have shown a close association between hypertension, obesity, IGT or NIDDM, and dyslipidemia. The activation of sympathetic nervous system plays a role in the pathogenesis of essential hypertension and its inhibition is of a therapeutic value. Rilmenidine is an oxazoline compound with antihypertensive properties that acts mainly on the brain stem but also in the kidneys, where it selectively binds to I1 imidazoline receptors, distinguishing it from reference α2-agonists. As a consequence, anti-hypertensive treatments that reduce the sympathetic response could also have effects on the metabolic abnormalities of hypertensive patients with metabolic disorders. The aim of the present study was to evaluate the effect of rilmenidine or placebo on insulin resistance and sympathetic activity, in essential hypertensive patients untreated or non-adequately treated. Our results have shown that Rilmenidine was able to decrease sympathetic activity expressed by both a decrease in SBP variability and an increase in baroreflex sensitivity. Together with these effects a significant improvement of insulin resistance index (HOMA), which was not obtained by the adjusted conventional treatment, was also observed. In conclusion, these beneficial effects observed support the idea that Rilmenidine could be comparable to established drugs for first-line therapy in hypertension.