The aim of this study is to investigate the cyclooxygenase (COX)-2 expression in esophageal epithelium of rat duodenoesophageal reflux model and the effect of a selective COX-2 inhibitor on esophageal adenocarcinogenesis in rats. A series of rats underwent a duodenoesophageal reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other group was given experimental chow containing nimesulide, a selective COX-2 inhibitor (nimesulide group). The animals were sacrificed sequentially after surgery and esophageal examinations were performed. In the control group, esophagitis, Barrett's esophagus (BE) and adenocarcinoma (EAC) were observed, and the frequency of these conditions increased with time. COX-2 expression, PGE(2) level and proliferative activity were up-regulated, predominantly in the inflamed esophageal epithelia, from the 10(th) week. In the nimesulide group, the esophagitis was mild and the frequency of BE was significantly lower than the control group, while EAC was not observed throughout the experiment. PGE(2) level and proliferative activity were lower in the nimesulide group than in the control group. COX-2 may play an important role in esophageal carcinogenesis through the activation of the inflammation-metaplasia-adenocarcinoma sequence. Nimesulide is effective in preventing BE and EAC by suppressing COX-2 activity.