Context: Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading to articular cartilage destruction. Shark cartilage polysaccharide (SCP) is a biodegradable, biocompatible, nontoxic, non-immunogenic and non-inflammatory polysaccharide that may be used in treating RA. Objective: The anti-RA activities of SCP given orally to rats are investigated here for the first time. Materials and methods: SCP treatment group were administered with SCP-1, SCP-2 in the dosage of 9 mg/day for 24 days. The effect of SCP-1 and SCP-2 on the body weight, paw swelling, morphological changes of ankle and IL-6, IL-12 secretion in RA rats are examined. Results: On day 24, there were no obvious differences in BMI between positive, SCP-1 and SCP-2 group. The swelling degree of SCP-1 and SCP-2 group was less serious than model group. X-ray revealed that SCP-1, SCP-2 group owned normal joint alignment and more smooth and tidy articular surface. The SCP-1 and SCP-2 have inhibitory effect on IL-6 (430.3 +/- 25.6 pg/mL, 439.1 +/- 35.9 pg/mL) and IL-12 (63.9 +/- 20.1 pg/mL, 64.9 +/- 14.1 pg/mL) secretion, which showed significant differences with model group (612 +/- 72.3 pg/mL, 230.1 +/- 29.2 pg/mL), but still higher than normal group (361.8 +/- 47.1 pg/mL, 34.2 +/- 15.1 pg/mL) and lower than positive group (418.1 +/- 42.5 pg/mL, 90.2 +/- 17.8 pg/mL). Especially, when the concentration of SCP was 125 mu g/mL, the contents of IL-6 (431.1 +/- 43.3 pg/mL, 401.7 +/- 55.7 pg/mL) and IL-12 (63.2 +/- 12.3 pg/mL, 52.3 +/- 8.7 pg/mL) were lowest. Discussion and conclusion: These findings demonstrate that SCP have excellent anti-RA activities and thus have great potential as a drug for treating RA diseases.