Zaocys type II collagen is an active collagen extracted from Zaocys that has been used to treat rheumatoid arthritis in China for over 1000 years. However, the mechanism still remains unknown. Therefore, we set out to investigate the inhibitory effect and possible mechanism of action of zaocys type II collagen on collagen-induced arthritis.Collagen-induced arthritis was induced in C57BL/6 mice by immunisation with type II collagen. After immunisation, the mice were treated with Zaocys type II collagen. Clinical and histological scores were assessed and the cytokine levels in the serum and lymphocytes supernatant from the spleen and mesenteric lymph node were determined by enzyme-linked immune sorbent assay. The T-helper 17 cell and regulatory-T cell frequencies were analysed by flow cytometry and the expression of interest markers was examined by direct immuno-fluorescence.The arthritis score and severity of histological inflammation and cartilage destruction were dose-dependently reduced after treatment. The analysis results indicated that Zaocys type II collagen significantly increased the proportion of regulatory-T cells and lowered the T-helper 17 cells, it also increased the number of regulatory-T cells and conversely decreased the T-helper 17 cells in synovial tissue compared with the model group. Treatment also caused a higher level of transforming growth factor-β and a decreased production of interleukin -17A.The oral administration of Zaocys type II collagen potently suppressed the severity of collagen-induced arthritis by repairing the imbalance between regulatory-T cells and T-helper 17 cells, suggesting that it might be a promising candidate for the treatment of rheumatoid arthritis.