〔Abstract〕 Objective To investigate the anti-inflammatory effect of polysaccharide from atractylodes atractylodes(PAMK) on rheumatoid arthritis(RA) rats and its effect on Toll like receptor 4/nuclear factor kappa-B(TLR4/NF-κB) signaling pathway. Methods RA rat model was induced by type Ⅱ collagen, after successful modeling, the rats were divided into model group, positive drug group(Tripterygium wilfordii polyglycoside tablet), PAMK low-dose and high-dose groups, normal control group was also set, with 12 rats in each group. Tripterygium wilfordii polyglycoside tablets or Atractylodes macrocephala polysaccharide were administered intragastric administration, once a day for 4 weeks. The body weight, paw swelling rate and arthritis index of rats were measured; the thymus index and spleen index were calculated; HE staining was used to observe the histopathological changes of synovial membrane of ankle joint; The levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in serum and synovial tissue of ankle were determined by ELISA; The expression levels of total protein TLR4, MyD88, phosphorylated NF-κB p65(Ser536) and nuclear protein NF-κB p65 in synovial tissue of ankle were detected by Western blot. Results Compared with the normal control group, synovial hyperplasia and unclear layers were observed in the model group, body weight decreased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index increased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle increased(P<0.05). Compared with model group, the histomathological changes of synovial of ankle joint in positive drug group and PAMK high-dose group were significantly improved, body weight increased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index decreased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle decreased(P<0.05), however, there were no significant differences in the above indexes between PAMK low-dose group and model group(P>0.05). Conclusion PAMK can reduce the inflammatory response and improve RA, and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway activation.