Peritoneal morphology and function are abnormal in uremia patients, but the contributing mechanisms are unclear. Here we attempted to characterize the protein targets that may be related to peritoneal change in patients with uremia and have not exposed to peritoneal dialysis fluid. Protein profiles of peritoneal fluids collected from patients with uremia and patients with normal renal function receiving laparoscopic cholecystectomy were displayed by two-dimensional gel electrophoresis (2-DE). Altered protein spots were excised and subjected to tryptic digestion followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Sixteen 2-DE protein spots were altered between two groups. Western blots confirmed that kininogen-1, apoptosis inhibitor 2, cat eye syndrome critical region protein 1, and apolipoprotein A-I had higher expression levels in the uremia samples. In contrast, synaptic vesicle 2-related protein, glial fibrillary acidic protein, and envelope glycoprotein (C2-V5 region) showed lower levels. The increased expression may result from a change in the permeability of the peritoneal membrane to middle-sized proteins or peritoneal inflammation with proteins sloughing off. All the identified proteins may provide a novel understanding of peritoneal changes caused by uremic toxins and may function as biomarkers or drug targets. (C) 2012 Elsevier B.V. All rights reserved.