Nuclear factor kappa beta (NF-κB) inhibits apoptosis in sensory, hippocampal, and striatal neurons of the central nervous system. Although several apoptotic stimuli have been shown to activate NF-κB in oligodendrocytes, the function of NF-κB in this cell type remains unknown. In this study, we introduced plasmids expressing either the p50- or p65-subunit of human NF-κB into Central Glia-4 (CG-4)—a rat oligodendrocyte precursor cell line—and determined the influence of NF-κB function on tumor necrosis factor-α (TNF-α)-induced apoptosis. Expression of NF-κB markedly prevented CG-4 apoptosis, with p50 being more effective than p65. This anti-apoptotic activity was repressed by IκB-α, an inhibitor of NF-κB. These results imply that NF-κB acts as a potent inhibitor of TNF-induced apoptosis in oligodendrocytes.