Objective: PB was excised when patients were undergoing catheter removal and controls for elective cholecystectomy. HPFBs were incubated with TGF-β1 (10 ng/ml) for 1 hour, later with TGF-β1 (10 ng/ml) and [Sildenafil (10µM) plus SB204741 (1µM)] for 24 hours (post-treatment strategy). In pre-treatment strategy, HPFBs were pre-treated with [Sildenafil (10 µM) plus SB204741 (1 µM)] for 1 hour and later with only TGF-β1 (10 ng/ml) for 24 hours. Similar strategies were followed for individual treatments of inhibitors. Real time qPCR for pro-fibrotic genes, collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), smooth muscle alpha (α)-2 actin (ACTA2), connective tissue growth factor (CTGF) and fibronectin1 (FN1) and anti-fibrotic genes, tissue inhibitor of metalloproteinases1 (TIMP1), matrix metalloproteinase2 (MMP2) was performed. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was housekeeping gene. Type 1 collagen and α-SMA proteins were examined by immunoblotting Methods: In TGF-β1 stimulated HPFBs, significant up-regulation of pro-fibrotic genes expression was observed, which significantly reduced on co-culture with PDE-5 plus 5-HT2B inhibitors. Ratio of anti-fibrotic genes (MMP2/TIMP1) was restored significantly. Expression of type 1 collagen was decreased significantly. Furthermore, near complete amelioration of ACTA2 as well as α-SMA protein was observed significantly (Table 1). Results: Dual inhibition combination of PDE-5 plus 5-HT2Binhibitors lead to near complete abrogation of conversion of resident fibroblasts to MFBs and thus may have the prospective for treatment of fibrosis of peritoneum in CAPD patients. Conclusions: Objective: Peritoneal fibrosis (PF) leads to ultrafiltration failure in patients during long-term continuous ambulatory peritoneal dialysis (CAPD). Serotonin (5-HT; 5-Hydroxytryptamine) produces extracellular matrix (ECM) proteins in transforming growth factor beta 1 (TGF-β1) dependent manner.  Here we evaluate the anti-fibrotic efficacy of phosphodiesterase-5 (PDE-5) inhibitor, Sildenafil, and 5-HT2B inhibitor, SB204741, in combination on human peritoneal fibroblasts (HPFBs) isolated from parietal peritoneum biopsy of CAPD patients.   Methods: PB was excised when patients were undergoing catheter removal and controls for elective cholecystectomy. HPFBs were incubated with TGF-β1 (10 ng/ml) for 1 hour, later with TGF-β1 (10 ng/ml) and [Sildenafil (10µM) plus SB204741 (1µM)] for 24 hours (post-treatment strategy). In pre-treatment strategy, HPFBs were pre-treated with [Sildenafil (10 µM) plus SB204741 (1 µM)] for 1 hour and later with only TGF-β1 (10 ng/ml) for 24 hours. Similar strategies were followed for individual treatments of inhibitors. Real time qPCR for pro-fibrotic genes, collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), smooth muscle alpha (α)-2 actin (ACTA2), connective tissue growth factor (CTGF) and fibronectin1 (FN1) and anti-fibrotic genes, tissue inhibitor of metalloproteinases1 (TIMP1), matrix metalloproteinase2 (MMP2) was performed. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was housekeeping gene. Type 1 collagen and α-SMA proteins were examined by immunoblotting Results: In TGF-β1 stimulated HPFBs, significant up-regulation of pro-fibrotic genes expression was observed, which significantly reduced on co-culture with PDE-5 plus 5-HT2B inhibitors. Ratio of anti-fibrotic genes (MMP2/TIMP1) was restored significantly. Expression of type 1 collagen was decreased significantly. Furthermore, near complete amelioration of ACTA2 as well as α-SMA protein was observed significantly (Table 1). Conclusions: Dual inhibition combination of PDE-5 plus 5-HT2Binhibitors lead to near complete abrogation of conversion of resident fibroblasts to MFBs and thus may have the prospective for treatment of fibrosis of peritoneum in CAPD patients.