Background Gastroesophageal reflux disease (GERD) is a common disorder. Dilation of intercellular spaces of esophageal epithelium has been revealed at transmission electron microscopy both in the rabbit acid-perfused esophagus and in esophageal biopsies from GERD patients. This study aimed to observe the changes of the intercellular spaces of squamous epithelium of lower esophagus in patients with GERD and the changes of intercellular spaces of patients with erosive esophagitis (EE) before and after omeprazole treatment.Methods Outpatients having GERD symptoms for more than 3 months and volunteers were collected. All of them underwent gastroendoscopy and 24-hour ambulatory pH monitoring. Biopsies were taken from the lower esophagus (2 cm above Z-line) for electron microscope examination. Five healthy volunteers, six non-erosive reflux disease (NERD) patients, and five EE patients were enrolled. Intercellular spaces of GERD patients and controls were calculated. Then we selected 20 patients with EE diagnosed by gastroendoscopy. All of them were treated with omeprazole (Losec, 20 mg bid) for 4 weeks then underwent gastroendoscopy again. Biopsies were taken from 2 cm above Z-line for electron microscope examination. All the patients completed the questionnaire about reflux symptoms before and after treatment.Results Intercellular spaces of esophageal epithelial cell in volunteers, NERD patients and EE patients were (0.37±0.07) μm, (1.31±0.08) μm, and (1.33±0.14) μm, respectively, with significant differences between the control group and the NERD group (P=0.000). In the 20 EE patients, the mean intercellular space before treatment was (1.14±0.15) μm. After treatment the intercellular space was (0.51±0.18) μm, a significant difference compared with pre-treatment measurements (P=0.000).Conclusions Dilated intercellular spaces (DIS) were seen in both NERD and EE cases. The dilated intercellularspaces of esophageal epithelium in EE patients could be recovered after a short time of treatment with omeprazole.