In the recurrence of allergic inflammation in a rat air pouch model, pouch fluid volume, prostaglandin E2 concentration in the pouch fluid, leukocyte infiltration into the pouch fluid, and granulation tissue weight were markedly increased by the antigen challenge. To clarify the role of cyclooxygenase-2 in the recurrence of allergic inflammation, the time-course of changes in protein levels of cyclooxygenase-1 and cyclooxygenase-2 in the granulation tissue and in the infiltrated leukocytes was examined by Western blot analysis. It was shown that cyclooxygenase-1 levels in the granulation tissue and in the infiltrated leukocytes were not changed by the antigen challenge, but cyclooxygenase-2 levels were increased. Furthermore, treatment with the selective cyclooxygenase-2 inhibitor, NS-398 ([N-2(cyclohexyloxy-4-nitrophenyl]-methanesulfonamide), suppressed the recurrence of allergic inflammation as did the non-selective cyclooxygenase-1/cyclooxygenase-2 inhibitor, indomethacin. The steroidal anti-inflammatory drug, dexamethasone, inhibited the induction of cyclooxygenase-2, and suppressed the allergic inflammation. These findings strongly suggested that cyclooxygenase-2 induced by the antigen challenge plays a role in the recurrence of inflammation induced by the allergic mechanism.