Abstract. Puerarin is an important active ingredient in the root of kudzu vine due to its pharmacological properties. The aim of the present study is to contribute to the existing knowledge of the effect of puerarin in the attenuation of inflammation and oxidation in mice with collagen antibody-induced arthritis via toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling. Arthritis was induced using injection of anti-type II collagen antibodies. Treatment with puerarin was observed to significantly decrease clinical scoring of the collagen antibody-induced arthritis and suppress oxidative stress and the inflammatory response in mice. Furthermore, puerarin was demonstrated to inhibit mRNA expression of matrix metalloproteinase-9 and protein expression of TLR4 following collagen antibody-induced arthritis in mice. The effect of puerarin may be associated with the suppression of NF-κB activity in collagen antibody-induced arthritis mice. Furthermore, upregulation of phosphorylated (p)-Janus kinase 2 and p-signal transducer and activator of transcription 3 protein expression was suppressed by puerarin. The results of the present study indicate, for the first time, the effect of puerarin to attenuate inflammation and oxidation in mice with collagen antibody-induced arthritis via TLR4/NF-κB signaling.