GABAergic projection from thalamic reticular nucleus to thalamic nucleus submedius in the medial thalamus of the rat was studied by using immunohistochemistry for GABA, retrograde labeling with Fluoro-Gold combined with immunohistochemistry for GABA, and anterograde labeling with biotinylated dextranamine. Immunohistochemistry displayed that only GABA immunoreactive terminals were observed in the thalamic nucleus submedius, while GABA immunoreactive neuronal cell bodies were located in the thalamic reticular nucleus and lateral geniculate nucleus. Injection of Fluoro-Gold into the thalamic nucleus submedius resulted in massive retrogradely labeled neuronal cell bodies in the rostroventral portion of the ipsilateral thalamic reticular nucleus and a few in the contralateral thalamic reticular nucleus, and most of these cell bodies showed GABA immunopositive staining. Many biotinylated dextranamine anterogradely labeled fibers and terminals in the thalamic nucleus submedius were observed after injection of biotinylated dextranamine into the thalamic reticular nucleus. The present results provide a morphological evidence for a hypothesis that a disinhibitory effect on output neurons elicited by opioid or 5-hydroxytryptamine inhibiting a GABAergic terminal in the thalamic nucleus submedius may lead to activation of the descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.