Inflammation responses and oxidative stress are closely involved in the pathogenesis of arthritis. Ligustrazine (Lig), a natural four methyl which is isolated from Chinese herb ligusticum chuanxiong hort, has been proved significantly anti-inflammation and anti-oxidative stress effects. The present study aimed to evaluate the effect of Lig on inflammation and oxidative stress in Freund's complete adjuvant (FCA)-induced arthritis in rats. The treatment of Lig significantly decreased the hind-paw volume change and alleviated the histopathological changes in sections of rat paws induced by arthritis. Lig also reduced the serum levels of pro-inflammatory cytokines (interleukin [IL]-6, IL-1 beta, and tumor necrosis factor-alpha), increased the activity of superoxide dismutase (SOD) and reduced the concentration of malondialdehyde (MDA). Besides that, the protein expressions of the sirtuin 1 (Sirt1)/nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf-2)/heme oxygenase (HO)-1 pathways determined by western bolt further confirmed that Lig effectively inhibited the Sirt1/NF-κB pathway and activated the Nrf-2/HO-1 pathway. Taken together, our results suggest Lig has therapeutic potential for arthritis, which might be via the regulation of Sirt1/NF-κB and Nrf-2/HO-1 pathways.