Scutellarin is the major effective constituent of the commonly used Chinese medicine Erigeron breviscapus. It has been applied in the clinic to treat various diseases, and is characterized by high content, a stable source, controllable quality, high efficiency and low toxicity. In addition, its potential pharmacological effects have been increasingly identified and elucidated. The present study was performed to examine the role of scutellarin on collagen-induced arthritis (CIA). Mice were injected subcutaneously with bovine collagen type II and administered scutellarin for 2 weeks by gavage 20 mg/kg/day. ELISA kits were used to measure the levels of interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), oxidative stress markers [superoxide dismutase (SOD) and malondialdehyde (MDA)] and caspase-3/-9 activity. Bax, Bcl-2, toll like receptor 4 (TLR4) and nuclear factor (NF)-kappa B protein expression was analyzed using western immunoblot analyses. The present study demonstrated that scutellarin prevented CIA, and inhibited the expression of inflammation factors, IL-1 beta, IL-6 and TNF-a. In addition, scutellarin reduced the levels of oxidative stress markers, SOD and MDA, as well as intercellular adhesion molecule-1 and monocyte chemoattractant protein 1 in CIA mice. Caspase-3/-9, Bax/Bcl-2, TLR4 and NF-kappa B protein expression were reduced in CIA mice following scutellarin treatment. The results of the current study suggest a novel effect of scutellarin involving the inhibition of TLR4/NF-kappa B-mediated inflammation.