This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.