Abstract: Objective To assess the clinical application value of impedance monitoring in the evaluation of mucosal barrier function by correlation analysis between esophageal impedance baseline and acid exposure, epithelial intercellular spaces (ICS) in patients with non-erosive reflux diseases (NERD). Methods A total of 46 NERD patients admitted to China-Japan Friendship Hospital from 2013 to 2014 and 18 healthy controls were enrolled in the study. All patients bad underwent 24 h pH-impedance monitoring and gastroendoscopy one week apart. Two biopsies were taken from the distal esophageal walls and ICS was quantified by histochemical technique. Results Patients with NERD had longer acid exposure time 4.1 (0.2 - 0.6)% vs 0.4 (1.0 - 5.3)%, P< 0.001, lower impedance baseline of distal esophagus (2 943±759)Ω vs (3 968±1076)Ω, P< 0.001 and wider ICS (1.01±0.20)μm vs (0.67±0.14)μm, P< 0.001 than controls. Baseline impedance was negatively correlated with AET (r=-0.35, P=0.016) and ICS (r=-0.58, P=0.002) in NERD patients. Conclusion The decrease of distal esophageal impedance baseline in NERD is associated with acid exposure and dilated intercellular spaces. Impedance monitoring can be used to assess esophageal mucosal integrity.