This study is performed to detect changes of gene expression in substantia nigra (SN) and striatum in manganese (Mn)-exposed mice brain. The cDNA array is a recently developed molecular biological method that can detect the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of trace metal intoxication effect at the genetic level. Using this technology, we discovered 5 genes in the mouse striatum and 9 genes in SN changed by more than 50% following Mn exposure. Depression were observed in two genes (neural cell adhesion protein BIG2, heavy neurofilament subunit genes) in striatum and three genes (light neurofilament subunit, brain acyl-CoA synthetase II, heavy neurofilament subunit genes) in the SN. However three genes (N-acetylglucosaminyltransferase I, S100β β β β β, and synaptonemal complex protein I genes) in striatum and six genes (noggin, striatin, Ost oncogene, S100β β β β β, calcium/calmodulindependent protein kinase kinase beta, and N-acetylglucosaminyltransferase I genes) in SN were elevated following Mn exposure. Immunohistochemical study revealed that protein levels of S100β β β β β also increased following Mn treatment. Activated astrocytes overexpressing S100β β β β β are invariably and intimately associated with decreased expression of heavy and light neurofilament subunits which is a distinguishing feature of neurodegeneration by Mn exposure. All our findings suggested that neuronal degenerations occur in SN as well as striatum of mice exposed to Mn.