Objective: Biopsy from parietal peritoneum (PB) of control patients (n=8) and CAPD patients (n=6) excised during laparotomy was incubated overnight in dispase (2.4 U/mL)/37°C.In post-treatment strategy, HPFBs isolated from CAPD patients and controls,were incubated with 5-HT (1µM)/TGF-β1 (10ng/ml) for 1 hour and later with 5-HT (1µM)/TGF-β1 (10ng/ml) and terguride or SB204741 (1µM, each) for 24 hours. , cells were pre-treated with terguride or SB204741 (1µM, each) for 1 hour and later with only 5-HT (1µM)/TGF-β1 (10ng/ml) for 24 hours (pre-treatment strategy).Real time quantitative PCR for pro-fibrotic (TGFΒ1, COL1A1, COL1A2, ACTA2, CTGFand FN1) and anti-fibrotic genes (MMP2/TIMP1) expression was performed. Type I collagen and α-SMA, phosphorylation status of Smad-3, ERK1/2, Src and STAT-3 was examined by western blotting. Methods: In 5-HT and TGF-β1stimulated HPFB, upregulated expression of COL1A1, COL1A2, ACTA2, CTGF and FN1(p<0.05) mRNA at 24 hr was observed. Co-culture of HPFB with 5-HT2and 5-HT2Breceptor antagonistssignificantly reduced pro-fibrotic genes expression (p<0.05) in both the strategies. Effect on anti-fibrotic genes mRNA in both the strategies was not affected. 5-HT dose-dependently increased the mRNA levels of TGF-Β1. Terguride and SB204741 mitigated alpha smooth muscle actin protein levels (figure 1) but they did not influenced Smad3 phosphorylation (canonical pathway, figure 2) rather they significantly reduced STAT3 phosphorylation (non-canonical pathway, figure 3) (p<0.05). However no effect on Src phosphorylation (figure 4) was observed. Results: TGF-β1 mediated ERK1/2/STAT3 pathways have been implicated in pro-fibrotic genes regulation in PF and 5-HT receptor antagonists attenuate 5-HT/TGF-β1 mediated pro-fibrotic potential of HPFBs.   Conclusions: Objective: Peritoneal fibrosis (PF) results in ultrafiltration failure in patients on long term continuous ambulatory peritoneal dialysis (CAPD). 5-hydroxytryptamine (5-HT; serotonin) induces extracellular matrix (ECM) synthesis  in a transforming growth factor beta 1 (TGF-β1) dependent manner. We evaluated anti-fibrotic role of inhibitors of 5-HT2(Terguride) and 5-HT2B(SB204741) in  in human peritoneal fibroblasts (HPFBs) isolated from peritoneum of CAPD patients . Methods: Biopsy from parietal peritoneum (PB) of control patients (n=8) and CAPD patients (n=6) excised during laparotomy was incubated overnight in dispase (2.4 U/mL)/37°C.In post-treatment strategy, HPFBs isolated from CAPD patients and controls,were incubated with 5-HT (1µM)/TGF-β1 (10ng/ml) for 1 hour and later with 5-HT (1µM)/TGF-β1 (10ng/ml) and terguride or SB204741 (1µM, each) for 24 hours. , cells were pre-treated with terguride or SB204741 (1µM, each) for 1 hour and later with only 5-HT (1µM)/TGF-β1 (10ng/ml) for 24 hours (pre-treatment strategy).Real time quantitative PCR for pro-fibrotic (TGFΒ1, COL1A1, COL1A2, ACTA2, CTGFand FN1) and anti-fibrotic genes (MMP2/TIMP1) expression was performed. Type I collagen and α-SMA, phosphorylation status of Smad-3, ERK1/2, Src and STAT-3 was examined by western blotting. Results: In 5-HT and TGF-β1stimulated HPFB, upregulated expression of COL1A1, COL1A2, ACTA2, CTGF and FN1(p<0.05) mRNA at 24 hr was observed. Co-culture of HPFB with 5-HT2and 5-HT2Breceptor antagonistssignificantly reduced pro-fibrotic genes expression (p<0.05) in both the strategies. Effect on anti-fibrotic genes mRNA in both the strategies was not affected. 5-HT dose-dependently increased the mRNA levels of TGF-Β1. Terguride and SB204741 mitigated alpha smooth muscle actin protein levels (figure 1) but they did not influenced Smad3 phosphorylation (canonical pathway, figure 2) rather they significantly reduced STAT3 phosphorylation (non-canonical pathway, figure 3) (p<0.05). However no effect on Src phosphorylation (figure 4) was observed. Conclusions: TGF-β1 mediated ERK1/2/STAT3 pathways have been implicated in pro-fibrotic genes regulation in PF and 5-HT receptor antagonists attenuate 5-HT/TGF-β1 mediated pro-fibrotic potential of HPFBs.