In the last 15 years a role has been ascribed for the medullary dorsal reticular nucleus as a supraspinal pain modulating area. The medullary dorsal reticular nucleus is reciprocally connected with the spinal dorsal horn, is populated mainly by nociceptive neurons and regulates spinal nociceptive processing. Here we analyze the distribution of brain projections from the medullary dorsal reticular nucleus using the iontophoretic administration of the anterograde tracer biotinylated-dextran amine and the retrograde tracer cholera toxin subunit B. Fibers and terminal boutons labeled from the medullary dorsal reticular nucleus were located predominately in the brainstem, although extending also to the forebrain. In the medulla oblongata, anterograde labeling was observed in the orofacial motor nuclei, inferior olive, caudal ventrolateral medulla, rostral ventromedial medulla, nucleus tractus solitarius and most of the reticular formation. Labeling at the pons-cerebellum level was present in the locus coeruleus, A5 and A7 noradrenergic cell groups, parabrachial and deep cerebellar nuclei, whereas in the mesencephalon it was located in the periaqueductal gray matter, deep mesencephalic, oculomotor and anterior pretectal nuclei, and substantia nigra. In the diencephalon, fibers and terminal boutons were found mainly in the parafascicular, ventromedial, and posterior thalamic nuclei and in the arcuate, lateral, posterior, peri- and paraventricular hypothalamic areas. Telencephalic labeling was consistent but less intense and concentrated in the septal nuclei, globus pallidus and amygdala. The well-known role of the medullary dorsal reticular nucleus in nociception and its pattern of brain projections in rats suggests that the nucleus is possibly implicated in the modulation of: (i) the ascending nociceptive transmission involved in the motivational-affective dimension of pain; (ii) the endogenous supraspinal pain control system centered in the periaqueductal gray matter–rostral ventromedial medulla–spinal cord circuitry; (iii) the motor reactions associated with pain.