TNF-$alpha$ elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-$alpha$ induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-$alpha$. TNF-$alpha$ initiates various signal transduction pathways leading to the activation of the caspase family, NF-${kappa}B$, Jun N-terminal kinase, and p38 MAPK via the death domain that contains the TNF-$alpha$ receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-$alpha$. This implies that the induction of anti-apoptotic genes for survival by TNF-$alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic genes for survival by TNF-$alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-$alpha$. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-$alpha$ in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-$alpha$ slowly increased and lasted several hours in the PC12 cell and DRG neuron. This specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-$alpha$ in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in resoonse to TNF-$alpha$ in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.