Background: Addition of nitroprusside, a nitric oxide (NO) donor, to peritoneal solution could enlarge both effective surface area and peritoneal pore size, leading to increased clearance of all solutes, Generalized usage of nitroprusside in CAPD patients, however, is not practical because it has very short half-life and need specific route of administration. Organic nitrates, another nitric oxide donor, had a longer half-life and easier absorbability via many routes. Objective: The present study was conducted to determine the effect and mechanism of oral active nitrate (isosorbide 5-mononitrate: ISMN) on solute and fluid transports in stable CAPD patients. Patients and Methods: A prospective randomized placebo control with cross over study was performed in 9 stable CAPD patients. In group1 (n=4), the treatment included 1) oral ISMN at the dose of 20 mg bid for 5 days 2) wash out period for 7 days and 3) placebo for 5 days. In group2 (n=5), the treatment regimens were placebo, wash out, and ISMN periods, respectively. Resultss The results showed that the MTACs of low molecular weight (LMW) solutes in ISMN period were greater than the placebo period: median urea, 16.65 vs. 13.75 ml/min; creatinine 7.88 vs. 6.91 ml/min, and urate 6.07 vs. 5.46 ml/min (P<0.05 for all except MTAC of urate). Administration of ISMN could also enhance the clearance of macromolecules with magnitude of increase as following: 10% for B2 microglobulin, 50% for albumin, and 15% for immunoglobulin G (P<0.05 for all). However, the restrictive coefficient (RC) of LMW solute as well as macromolecules of both group were similar, indicating that the increased solute transports were not due to alteration in the peritoneal membrane permeability. Despite the increased peritoneal solute clearance, net ultrafiltration was unchanged after drug administration, 110(ISMN group) vs. 120 ml(placebo group), (NS). Conclusion: As such, ISMN has similar effect as nitroprusside in enhancing peritoneal clearance of both small and large molecular weight solutes.This effect is mediated via expansion of peritoneal surface area. As such administration of oral ISMN to stable CAPD patients in beneficial in enhancing the achievement of target solute clearance suggested by NKF DOQI Guidelines.