The nuclear factor-κB (NF-κB) pathway is important in neuronal survival and in integration of external signals e.g. cytokines, glutamate, Aβ and nerve growth factor (NGF). During rat cerebellar development NF-κB activity is high in granule cells before postnatal day 7 (P7) and declines after P7. Using gene expression profiles, measured by cDNA arrays, up-regulation of transforming growth factor-beta2 (TGF-β2) was correlated with the developmental down-regulation of NF-κB. TGF-β2 depicted strongest, more than 4-fold, up-regulation in P12 versus P4 cerebella. In situ hybridization and immunohistochemistry confined upregulated TGF-β2 to granule cells and correlated mRNA and TGF-β2-protein increase. Finally TGF-β2 repressed NF-κB activity, in an in vitro system resembling migrating cerebellar granule cells. Thus, TGF-β might fulfill an important role in repressing developmentally activated NF-κB in granule neurons.