Peritoneal membrane changes in continuous ambulatory peritoneal dialysis (CAPD) patients have been widely described but poorly classified. Our aim was to identify the morphological changes occurring after CAPD treatment. To this end, 17 biopsies of parietal peritoneum (1 cm in diameter) were withdrawn at least 5 cm from the catheter entry hole and stained with Van Gieson, hematoxylin-eosin, trichrome, and some immunohistochemical stains: keratin, vimentin, CD34, CD20, CD4, CD8, desmin, and collagen IV. The morphology of mesothelium, vessels, and basement membrane (BM) of mesothelium and vessels, the presence of inflammatory cells, fibrin, and calcifications, and the distribution and thickness of submesothelial tissue were evaluated. Patients were divided into three groups according to the thickness of the sclerotic band replacing mesothelium: group 1, band up to 40 microns; group 2, band less than 40 microns; group 3, no sclerotic band. The main histopathological alterations noted were: loss of mesothelium; sclerotic alteration of vessels or duplication of BM; presence of myofibroblasts; and presence of inflammatory cells (sparse, focal, or perivascular), mainly represented by macrophages and CD4+ lymphocytes. No significant qualitative differences were observed between the three groups. In conclusion, the variable histological changes in peritoneal membrane suggest a routine peritoneal biopsy in any surgical procedure to better understand pathological changes in the course of CAPD treatment.