The aim of this study was to investigate the effects of pentylenetetrazol (PTZ) and nuclear factor kappa B (NF-kappa B) decoy oligodeoxynucleotides (ODNs) on p38 expression in neuron-like PC12 cells. In addition, the role of NF-kappa B activation in the pathogenesis of epilepsy was explored. p38 expression levels in control and PTZ-treated neuron-like PC12 cells were examined using western blotting. NF-kappa B decoy ODNs were transfected into the neuron-like PC12 cells using Lipofectamine 2000. NF-kappa B activation was investigated by confocal laser scanning microscopy (CLSM), and p38 expression levels were assessed using western blotting prior to and following transfection of decoy ODNs. Western blot analysis revealed that p38 levels in PTZ-treated neuron-like PC12 cells were significantly higher than those in control cells. CLSM demonstrated that the decoy ODNs inhibited NF-kappa B activation in neuron-like PC12 cells, and western blotting indicated that the decoy ODNs did not reduce p38 levels. The results of this study indicate that PTZ enhances p38 expression levels and activates NF-kappa B in PC12 cells. However, NF-kappa B does not modulate p38 expression levels.