The dorsal raphe (DR) nucleus is a system of nuclei in the midline of the lower brainstem, which is considered one of the most important nuclei in the modulation of pain in the central nervous system. Central noradrenergic systems play an important role in the control of cardiovascular regulation and pain transmission. Clonidine, an alpha 2-adrenergic agonist is used extensively in anesthesia research. In this study, we evaluated the involvement of clonidine in the activity of DR nucleus and its possible role in pain modulation. Seventy-four neurons within the DR nucleus in the rat brainstem slice preparation were tested using extracellular recording techniques. Application of noradrenaline (NA), 50 mumol/L, induced firing activity in 68 neurons tested (92%). NA produced a regular long-lasting firing activity on the DR neurons. Fifty-six neurons (88%) previously excited by NA were inhibited by clonidine, 20 mumol/L. Clonidine suppressed the firing activity of neurons. The results indicate that the firing of DR neurons was under noradrenergic influence and was inhibited by clonidine, which in turn alters nociception by modifying the central serotonergic system.