ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang is a famous Traditional Chinese medicine consisting of Rhizoma coptidis (Coptis chinensis Franch, Ranunculaceae), Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae), Cortex phellodendri (Phellodendron amurense Rupr. Rutaceae) and Fructus gardeniae (Gardenia jasminoide Ellis, Rubiaceae) in a weight ratio of 3:2:2:3.This formula was described by Wang Tao (in the Chinese Tang Dynasty) in his treatise "Wai Tai Mi Yao". It has been used to treat inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases in the clinical practice of Traditional Chinese medicine, especially in treating inflammation for nearly two thousand years. However, the essential compounds in it have not been identified, and the mechanisms remain to be addressed. To investigate the protective effects of HLJDT and its component group (HLJDT-CG) on collagen-induced arthritis in rats. MATERIALS AND METHODS: CIA was established in male Wistar rats with subcutaneous injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of HLJDT aqueous extracts (270 mg/kg) or HLJDT-CG (40 mg/kg) once per day from day 6 to day 28. Rats in normal and vehicle control groups were given an equal volume of vehicle (0.9% saline) and 0.025 mg/kg Dexamethasone was given to the Standard group at the same time. The protective effect of them were assessed by measuring arthritis index, swelling, the cytokines such as TNF-α, IFN-γ and IL-17 in serum, type II collagen antibodies, splenocyte proliferation and so on. RESULTS: The results demonstrated that treatment of CIA rat with either HLJDT aqueous extracts or HLJDT-CG not only ameliorated the symptoms of arthritis, prevented joint damage but also reduced the serum levels of TNF-α, IFN-γ and IL-17 in CIA rats. Anti-CII antibodies showed the similar trend except that of IgG1. Furthermore, HLJDT aqueous extracts and HLJDT-CG administration also suppressed CII-induced proliferative response of splenocytes. More importantly, HLJDT-CG exhibited similar pharmacological activities as HLJDT aqueous extracts in all aforementioned experiments. CONCLUSIONS: HLJDT aqueous extracts and HLJDT-CG could effectively ameliorate CII-induced arthritis and significantly suppress the immune response against CII with similar pharmacological efficacy. These findings suggest that HLJDT has therapeutic potential in RA treatment and HLJDT-CG can represent the effective-composite of HLJDT.