S100β is a soluble calcium binding protein released by glial cells. It has been reported as a neurotrophic factor that promotes neurite maturation and outgrowth during development. This protein also plays a role in axonal stability and in long term potentiation in the adult brain. The ability of S100β to modulate neuronal morphology raises the important question whether there is an age-related difference in the expression of S100β in the cerebral and cerebellar cortices of AKR strain mice and is this change is region specific. Our RT–PCR and Western blotting experiments show that the expression of S100β gene in the cerebral and cerebellar cortices starts from 0 day, peaks at about 45 days. However, in 70-week old mice its expression is significantly up-regulated as compared to that of 20-week old mice. S100β follows the same age-related pattern in both cerebral and cerebellar cortices. These results suggest that S100β is important for brain development and establishment of proper brain functions. Up-regulation of S100β in old age may have some role in development of age-related pathological systems in the brain.