Thioredoxins are a class of small redox-regulating proteins that have been implicated in the control of various aspects of cellular functions and seem to be one of the key regulators of signalling in the cellular responses to various stresses. Thioredoxin-2 (Trx2) is a novel mammalian thioredoxin which, in contrast to previously known cytosolic thioredoxin (Trx1), has been localized to the mitochondria. Trx2 is abundantly expressed in skeletal muscle, heart and adrenal gland, as well as in some other peripheral tissues with high metabolic activity. Using in situ hybridization and immunohistochemistry, we have studied the distribution and regulation of Trx2 expression in the rat brain. Trx2 mRNA and protein are highly expressed in the neurons in several brain regions, including the olfactory bulb, frontal cortex, hippocampus, some hypothalamic and thalamic nuclei, cerebellum and numerous brainstem nuclei. In addition, the Trx2 mRNA expression in paraventricular hypothalamic nucleus and reticular thalamic nucleus was found to be sensitive to peripheral glucocorticoids, as dexamethasone treatment caused significant elevation of Trx2 mRNA level in this area. No changes in other brain areas were observed after dexamethasone treatment. These findings implicate a significant regulatory and/or protective function of Trx2 in the nervous system.