Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction. In this study, we explored the effect of berberine on rats with bovine type II collagen-induced arthritis (CIA), an animal model for RA. Following treatment, berberine attenuates arthritic scores and suppresses collagen-specific immune responses in CIA rats. Compared with the un-treated CIA group, berberine reversed pathological changes, which showed a significant improvement in synovial hyperplasia and inflammatory infiltration. The expression levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-17 and vascular endothelial growth factor (VEGF) were obviously reduced in the sera of berberine-treated rats (all P < 0.05). Moreover, berberine showed marked inhibition of the expression of VEGF and CD34 (all P < 0.05). Interestingly, berberine significantly suppresses p-ERK, p-p38 and p-JNK activation (all P < 0.05), which may partially explain the anti-RA activity of berberine. These results suggest that berberine ameliorates CIA in rats associated with anti-inflammatory and anti-angiogenic effects, which might be of great therapeutic value for RA.