The ability of melatonin treatment of aged animals to partially restore the pattern of gene expression characterizing the younger animal has been frequently reported. The current study examines the effect of melatonin upon age-related changes of some key proteins relevant to the aging process. Male B6C3F1 mice, aged 5.5 months and 23.4 months were used as a model for aging and half of each group received a diet supplemented with 40-ppm (w/w) melatonin for 9.3 weeks. Protein components of the globus pallidus were studied including glial fibrillary acidic protein (GFAP), NF-κB, protein disulfide isomerase (PDI), and Nissl staining. Some age-related changes were in an upward direction (GFAP and NF-κB), while others were depressed with age (PDI and intensity of Nissl staining). However, in either case, melatonin treatment of aged mice generally altered these parameters so that they came to more closely resemble the levels found in younger animals. The extent of this reversal to a more youthful profile, ranged from complete (for NF-κB) to very minor (for Nissl staining and PDI). Overall, these findings are in accord with prior data on the effect of melatonin on cortical gene expression and confirm the value of melatonin as a means of retarding events associated with senescence.