Saposhnikovia divaricata (Trucz.) Schischk is a traditional Chinese herbal medicine that is widely used to regulate rheumatoid arthritis (RA). We extracted SD-a, a polysaccharide from S. divaricata , and analyzed its structure by chemical and spectral analysis. We further studied the anti-rheumatoid effect of SD-a in collagen-induced arthritis (CIA) rats and the molecular mechanism in RA fibroblast-like synoviocytes (RA-FLS). The results show that SD-a (MW 192.20 kDa) is composed of Man, GluA, GalA, Glu, Gal, and Ara, at a molar ratio of 4.16:1.97:37.46:2.12:16.42:37.87. Its main chain is →{[4)- α - D -GalA p -(1→5)- α - L -Ara f -(1→4)- α - D -GalA p -(1→5)- α - L -Ara f -(1→6)- β - D -Galp-(1] ₈ →3,6)- α - D -Man p -(1→3)- β - D -Man p -(1→4,6)- β - D -Glc p -(1} ₂₃ →. SD-a can significantly increase Bax and reduce Bcl-2 protein expression in RA-FLS, thus inducing apoptosis. It can also significantly inhibit the protein expression of matrix metalloproteinases 2/9 (MMP2/9) in RA-FLS, thereby inhibiting cell migration and invasion. Moreover, SD-a inhibited the course of RA in CIA rats by regulating the TLR4/TRAF6 – NF-κB/IκB-α pathway. The present study indicates that SD-a might be used for RA treatment.