Abstract: Objective To investigate the role of Phellinus Polysaccharide (PPS) in activating canonical Wnt signaling in rats with rheumatoid arthritis (RA). Methods Male SD rats were randomly divided into three groups (normal group, RA model group and PPS treated RA group), each with 10 rats. The RA model rats were prepared through intradermal injection of 0.1 mL complete Freund’s adjuvant into the right rear toes of the rats. The PPS treated RA rats were given 50 mg/kg PPS by gavage eight days after the introduction of RA. All rats were evaluated with arthritis score and paw swelling score at day 16, 20, 24, 28, 32. At day 28, the expressions of fibronectin gene, Wnt signal pathway negative regulation gene SFRP1,2 and Wnt key gene β-catenin, C-myc, and ccnd1 were detected by real time qPCR. Results PPS significantly reduced the arthritis score and paw swelling score of RA model rats. Lower levels of expression of SFRP1,2 and higher levels of expression of β-catenin, C-myc, ccnd1 and fibronectin were found in the RA model rats compared with the normal controls. PPS increased the expression of SFRP1,2 and decreased the expression of β-catenin, C-myc, ccnd1 and fibronectin in the RA rats. Conclusion PPS has significant therapeutic effect on RA model rats through inhibiting canonical Wnt signaling.