Inflammation responses and oxidative stress areclosely involved in the pathogenesis of arthritis. Ligustrazine(Lig), a natural four methyl which is isolated fromChinese herb ligusticum chuanxiong hort, has been provedsignificantly anti-inflammation and anti-oxidative stresseffects. The present study aimed to evaluate the effect ofLig on inflammation and oxidative stress in Freund’scomplete adjuvant (FCA)-induced arthritis in rats. Thetreatment of Lig significantly decreased the hind-pawvolume change and alleviated the histopathological changesin sections of rat paws induced by arthritis. Lig alsoreduced the serum levels of pro-inflammatory cytokines(interleukin [IL]-6, IL-1 beta, and tumor necrosis factoralpha),increased the activity of superoxide dismutase(SOD) and reduced the concentration of malondialdehyde(MDA). Besides that, the protein expressions of the sirtuin1 (Sirt1)/nuclear factor kappa B (NF-jB) and nuclearfactor (erythroid-derived 2)-like-2 factor (Nrf-2)/hemeoxygenase (HO)-1 pathways determined by western boltfurther confirmed that Lig effectively inhibited the Sirt1/NF-jB pathway and activated the Nrf-2/HO-1 pathway. Taken together, our results suggest Lig has therapeuticpotential for arthritis, which might be via the regulation ofSirt1/NF-jB and Nrf-2/HO-1 pathways.