Recent studies have shown that esophageal mucosal inflammatory response is involved in the pathophysiology of gastro-esophageal reflux disease. The aim of the present study was to identify specific gene expression profiles of the esophageal mucosa in a rat model of combined-type chronic reflux esophagitis. Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl-ether inhalation anesthesia. Esophageal epithelial cells were obtained from esophagi of rats by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the rat toxicology U34 GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating software, ingenuity pathway analysis software, and Gene Springs software. A comparison between esophagitis and sham-operated rats 2 weeks after the operation revealed that 368 probes (36%) were significantly affected, i.e. 185 probes were up-regulated, and 183 probes were down-regulated, both at levels of at least 1.5-fold in the esophagitis rats. Ingenuity signal analysis of 207 affected probes revealed the interleukin-6 signaling pathway as the most significantly affected caronical pathway. In addition, the expression of many genes associated with cytokine and transcription factor was enhanced in the esophagitis rats. This transcriptome approach provided insight into genes and putative genetic pathways thought to be affected by stimulation with gastroduodenal refluxates.