Peritoneal fibrosis (PF) is an important complication of long-term peritoneal dialysis. Although mineralocorticoid and its receptor have attracted increasing attention in the field of vascular injury, including the heart, kidney and vessels, little is known about the role of mineralocorticoid in PF. This work was designed to explore the effects of mineralocorticoid receptor (MR) blockade against PF. For this purpose, we developed a new model of PF in rats based on mechanically scraping the peritoneum. This model is characterized by acute-phase inflammation (neutrophil and macrophage infiltration on days 0-3) and late-phase PF (-smooth muscle actin-positive fibroblast infiltration, type III collagen accumulation, and neoangiogenesis on days 7-14). Peritoneal thickening peaked at day 14. MR was expressed in the rat peritoneum and rat fibroblast cell line. Expression of its effector kinase (Sgk1), transforming growth factor- (TGF-, plasminogen activator inhibitor-1 (PAI-1) and CD31-positive vessels increased during the course of PF. Rats were treated with Spironolactone, angiotensin receptor blockade (ARB) or angiotensin-converting enzyme inhibitor (ACE-I)/ARB/Spironolactone starting at 6 hours after peritoneal scraping. All parameters, including peritoneal thickening, number of macrophages and CD31-positive vessels, and expression of monocyte chemoattractant protein-1/TGF-/PAI-1/Sgk1, were significantly suppressed by Spironolactone (10 mg/kg/day). The effects of Spironolactone (10 and 20 mg/kg/day) were very similar to those of triple blockade. ARB, but not ACE-I, significantly reduced the peritoneal thickening. Furthermore, peritoneal function assessed by peritoneal equilibration test was significantly improved by Spironolactone. Our results suggest that MR is a potential target to prevent inflammation-induced peritoneal fibrosis in patients on peritoneal dialysis.