The aim of the study was to compare the electrophysiology profile of sheep pleura originated from different locations of the pleural cavity with the respective profile in humans. Sheep specimens obtained from upper and lower lung lobes, 1st-4th and 8th-12th rib, ventral-dorsal diaphragm and mediastinum were mounted between Ussing chambers. Human visceral tissues were obtained from patients subjected to lobectomy. Trans-mesothelial resistance (R(TM)) was determined as an indicator of the tissue permeability, while amiloride and ouabain were used as inhibitors of cellular transportation via ion transporters. Control values R(TM) were low in lower lobe visceral, caudal costal parietal and diaphragmatic pleura. Amiloride increased R(TM) at all locations except upper visceral and mediastinum. Higher R(TM) increases were found in caudal parietal and dorsal diaphragmatic samples. Ouabain increased R(TM) of lower visceral, caudal parietal and diaphragmatic pleura but not of mediastinal specimens. Observations made in sheep tissue were comparable with human visceral, parietal and mediastinal regions. In conclusion, results suggest heterogeneity of trans-mesothelial permeability among different pleural locations in sheep as was the case for humans. Thoracic surgeons should consider physiology function of each part of pleural cavity before pleural tissue manipulation. Observations made in sheep may be used to understand human physiology.