Curcumin is a natural herbal product that has been popularly used to treat autoimmune diseases in China; however, its effects on rheumatoid arthritis and its mechanism are not clear. The main purposes of this study are to explore the therapeutic effects of curcumin on collagen-induced arthritis (CIA) rats and the pharmacological mechanism. In the present study, CIA rats were established by injecting bovine type II collagen. Curcumin and methotrexate were then orally administered daily, and the swelling degree of the hind limb joints was scored every two days. Histopathological changes were observed by hematoxylin-eosin staining. The levels of cytokines (TNF-α, IL-1β, IL-17 and TGF-β) were detected by radioimmunoassay, while the expression of IκBα and COX-2 was detected by Western blot. In addition, cell viability was detected by CCK-8 assay, and the effect of curcumin on macrophage apoptosis was detected by flow cytometry and TUNEL assay. The results indicated that in vivo curcumin attenuated the degree of joint swelling of rats and the further development of joint histopathology. Moreover, it downregulated the levels of cytokines. In vitro curcumin inhibited the degradation of IκBα and reduced the production of COX-2 in LPS-induced inflammatory RAW264.7 cells. Importantly, curcumin significantly induced macrophage apoptosis. In conclusion, in this study, we have demonstrated that curcumin exerts therapeutic effects on arthritis in CIA rats and has a strong pharmacological activity on reducing the inflammatory response in macrophages. Its mechanism may be related to the inhibition of the NF-κB signaling pathway and the promotion of macrophage apoptosis. •Curcumin significantly attenuated inflammation in the joints of CIA rats and LPS-induced RAW264.7 cells;•Curcumin inhibited the level of TNF-α and IL-17 in synovial tissue and serum;•The mechanism might be related to inhibiting NF-κB signaling pathway and promoting macrophage apoptosis.