Pineal gland and its hormone melatonin have been implicated in modulation of cardiovascular system. We aimed at studying the effects of melatonin on baroreflex sensitivity and the role of area postrema, as a component modulator of baroreflex arch. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving rats. Baroreceptor reflex sensitivity was assessed by determining the HR responses to ramped infusions of phenylephrine (PE) and sodium nitroprusside (SNP)-induced MAP changes. Melatonin bolus (0.11 mg/kg) immediately followed by its continuous infusion (0.43 × 10−9 mol/L at a rate of 0.65 mL/h for 30 min) in healthy normotensive rats produced a downward shift of baroreceptor reflex control with a substantial inhibition of reflex tachycardia (−32%) and potentiation of reflex bradycardia (+20%). Ablation of area postrema (APX group) induced a sustained decrease of MAP (101 ± 3 vs. 116 ± 3 mmHg, P < 0.05 in comparison with sham rats, respectively). The melatonin-induced alterations of baroreflex function observed in the sham group were abolished in the APX group. We conclude that circulating melatonin can modulate baroreceptor reflex control of HR, thus resetting it toward lower HR values. The modulatory effects of melatonin may be mediated via melatonin receptors in the area postrema, located outside the blood–brain barrier.