Background and aim: We study the effects of melatonin and omepra-zole on rats with experimentally in­duced reflux esophagitis. Materials and methods: Sixty rats were divided into 12 sham operated rats and 48 rats with induced reflux esophagitis (RE), which were divided into either RE alone or pretreated by melatonin (MT), omeprazole or both, with or without inhibition of prosta-glandin (PG) generation by indometh-acin. Reflux esophagitis was induced in rats by ligating the pylorus and the junction between the forestomach and corpus. In all rats, gastric acid output, pH, nitric oxide (NO), melato­nin, esophageal PGE2, malondialde-hyde (MDA) and reduced glutathione (GSH) were measured. The esopha­geal injury was assessed by macro­scopic damage score, lesion length and microscopic regenerative epithe­lial changes and leucocytic infiltration scores. Results: Induction of RE in­creased gastric acid output, plasma NO, mucosal PGE2, MDA, decreased pH, plasma MT, GSH and caused esophageal mucosal injury. Indo-methacin administration to RE rats caused further increase in esopha­geal injury, acid output and decrease in pH and PGE₂. Pretreatrnent with omeprazole significantly increased pH, decreased acid output, and esophageal injury in comparison to MT p < sup>retreatment. In addition, MT pre-treatment induced significant increase