Aspirin has been proposed in recent years as a candidate for chemoprevention of adenocarcinoma in patients with Barrett's esophagus. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux was established using Wistar rats undergoing esophagojejunostomy with gastric preservation. Following surgery, rats were divided into three groups: i) control (vehicle); ii) ASA 50 mg/kg/day; and iii) ASA 5 mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E2 (PGE2) and lipoxin A4 (LXA4 ) levels] analysis. As in the control rats, those receiving aspirin treatment showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa, length of intestinal metaplasia in continuity with anastomosis, presence of intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal tissue levels of PGE2 and increased LXA4, significantly in the high-dose aspirin group (p=0.008 and p=0.01, respectively). In this rat model of gastroesophageal reflux, the administration of aspirin modified esophageal tissue levels of PGE2 and LXA4, but was not effective in preventing the development of esophageal adenocarcinoma.