beta-1,4-Galactosyltransferase-I (beta-1,4-GalT-I) is one of the best studied glycosyltransferases. Previous studies demonstrated that beta-1,4-GalT-I was a major galactosyltransferase responsible for selectin-ligand biosynthesis and that inflammatory responses of beta-1,4-GalT-I deficient mice were impaired. Our previous study suggest that beta-1,4-GalT-I may play an important role in regulating immune cell migration into the inflammatory site. In this study, we investigate beta-1,4-GalT-I may play an important role in mediating microgliosis. The results of this study demonstrated that beta-1,4-GalT-I was strongly induced in the ventral midbrain by intranigral injection of LPS. Most galactose-containing glycans and beta-1,4-GalT-I were expressed in microglia. Moreover, an Ab against beta-1,4-GalT-I attenuated both LPS-induced microglial activation and phagocytosis. We therefore suggest that beta-1,4-GalT-I may play an important role in regulating immune cell migration into the inflammatory site and mediating microgliosis.