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Background: Structure and function of the peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). The aim of this study was to examine the relationship between dialytic parameters and histological and functional characteristics of the peritoneum of PD patients., Methods: A peritoneal biopsy (PB) was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. PB was performed at least 5 cm from the catheter insertion. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies., Results: (1) Duration of treatment was longer in patients with mesothelial impairment. (2) Patients showing sub-mesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to a larger daily glucose load. (3) SS exceeding 50 mm was more frequent among high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. (4) Mesothelial loss correlated to SS and vascular alterations. (5) SS was related to vascular injuries but not to inflammatory infiltrate., Conclusions: SS is not constant in PD patients and is not a prominent factor in treatment drop-out. Mesothelial impairment seems to be mainly related to duration of PD treatment. Glucose load seems to mainly damage the sub-mesothelial layer.