To study the inflammatory hyperalgesia induced by an acute noxious stimulation of oral mucosa with 5% formalin (5%FOR), we performed an immunohistochemical study on the expression of TNFá in the intermolar region of the dorsal lingual eminence (IDLE), and Iba1 and phosphorylated (phospho)- p38 MAPK involved with central nervous system microglial activation in the trigeminal subnucleus caudalis (Vc). The present study observed significantly increased expression of TNFá at either 1h or 24h of 5%FOR nociception, as well as sustained TNFá immunoreactivity in the IDLE. On the other hand, at either 1h or 24h 5%FOR nociception, Iba1- immunoreactive (IR) cells in the Vc were significantly increased after inflammatory stimulation of the IDLE; the increase was more evident at 24h 5%FOR nociception. By using the double-label immunofluorescence technique, the findings in particular demonstrated a significant increase in the number of phospho-p38 MAPK- and Iba1-IR coexpressed cells in the Vc at 24h 5%FOR nociception. The results suggest that 24h persistent microglial activation in subnuclei zonalis and gelatinosus of the Vc is evoked by 5%FOR noxious stimulation of the IDLE oral mucosa, thereby the present study indicates that the MAPK expression plays important roles in microglial activation related with central sensitization and inflammatory hyperalgesia.