Objective: To explore the effect and mechanism of quercetin (quercetin, QCT) on peritoneal fibrosis (peritoneal fibrosis, PF) in peritoneal dialysis (peritoneal dialysis，PD) rats based on the Wnt/β-catenin pathway. Methods: A PD rat model was constructed, and successfully modeled rats were stochastically classified into PD group, QCT-L group, QCT-H group (gavage of 17.5 mg/kg, 35 mg/kg QCT), and QCT-H+LiCl group (gavage of 35 mg/kg QCT+intraperitoneal injection of 60 mg/kg Wnt/β-catenin signaling pathway activator LiCl). Another 12 rats were stochastically served as the Ctrl group. The Ctrl group and PD group were given an equal amount of physiological saline by gavage once a day for 4 weeks. The peritoneal balance test was used to assess peritoneal function. HE staining was performed to observe changes in peritoneal tissue. Masson staining was performed to observe peritoneal tissue fibrosis. ELISA method was performed to measure inflammatory factors (TNF-α, IL-1β, IL-6). IHC was used to detect the α-SMA, CoL-1, and E-cadherin proteins in rats. Western blot was performed to detect the Wnt3a, LRP5, LEF-1, GSK-3β and β-catenin proteins in rats. Results: Compared with the 0 mg/kg LiCl group, the 30 and 60 mg/kg LiCl groups showed no significant effects on renal and peritoneal functions (P>0.05), the levels of Scr, BUN, and MTG In the 90 mg/kg LiCl group significantly increased, while UF significantly decreased (P<0.05). In addition, the 30 mg/kg LiCl group exhibited no significant impact on Wnt3a, β-catenin protein expression (P>0.05), whereas the 60 and 90 mg/kg LiCl groups showed significant upregulation of Wnt3a and β-catenin protein expression (P<0.05). Therefore, 60 mg/kg was selected as the concentration of LiCl for activating the Wnt/β-catenin signaling pathway. Compared with the Ctrl group, the peritoneal mesothelial cells of rats in the PD group shed, with a large amount of collagen fiber deposition and prominent infiltration of inflammatory cells. The serum Scr, BUN levels, MTG, peritoneal thickness, peritoneal tissue TNF-α, IL-1β, IL-6 levels, α-SMA, CoL-1, Wnt3a, LRP5, LEF-1, β-catenin proteins increased (P<0.05), while UF, E-cadherin and GSK-3β protein decreased (P<0.05). Compared with the PD group, the QCT-L and QCT-H groups showed a small amount of mesothelial cell shedding, reduced collagen fiber deposition, and infiltration of inflammatory cells in the peritoneal tissue. The serum Scr, BUN levels, MTG, peritoneal thickness, peritoneal tissue TNF-α, IL-1β, IL-6 levels, α-SMA, CoL-1, Wnt3a, LRP5, LEF-1, β-catenin proteins decreased (P<0.05), while UF, E-cadherin, and GSK-3β protein increased (P<0.05). Compared with the QCT-H group, the QCT-H+LiCl group showed a prominently increased degree of peritoneal tissue damage. The serum Scr, BUN levels, MTG, peritoneal thickness, peritoneal tissue TNF-α, IL-1β, IL-6 levels, α-SMA, CoL-1, Wnt3a, LRP5, LEF-1, β-catenin proteins increased (P<0.05), while UF, E-cadherin and GSK-3β protein decreased (P<0.05). Conclusion: QCT alleviates PF in PD rats by inhibiting inflammatory response and peritoneal mesothelial cell mesenchymal transition process, and its mechanism of action may be related to the inhibition of Wnt/β-catenin signaling pathway.