Background & Aims: The role of two forms of cyclooxygenase (COX-1 and COX-2) in gastric mucosal lesions is not well understood, The regulation of both forms of COX and the effect of COX-2 on the repair process of gastric mucosal lesions in mice were investigated, Methods: Gastric mucosal erosions and ulcers were induced experimentally in mice. The level of COX messenger RNA (mRNA) was determined by reverse-transcription polymerase chain reaction, COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist. The effects of long-term administration of NS-398 on gastric ulcers were examined, Results: COX-2 mRNA levels were not detected in control conditions but were high during the acute stages of gastric erosions and ulcers, COX-2 protein was detected 5 days after ulcer induction but not in control mice, Gastric ulceration was not associated with a change in COX-1 mRNA and protein levels, Administration of NS-398 to mice with ulcers at acute stages impaired the healing of ulcers, Conclusions: High levels of COX-2 mRNA and protein during the acute stages of gastric mucosal lesions may be involved in the repair process of these lesions in mice.