Introduction: Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats. Methods: 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 nil isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated. Results: Although the MMF and resting groups showed beneficial effects on ultrafiltration and D-1/D-0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGF-beta 1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm(2) of submesothelial area, decreased in the treatment group. Conclusions: MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.