To study the effect of carboxyamidotriazole (CAI) on adjuvant arthritis (AA) in rats. The rats were randomly divided into normal group,two vehicle groups (polyethylene glycol 400 control and normal sodium control group), CAI-treated groups (10, 20, and 40 mg/kg) and positive control dexamethasone group. Freund's completed adjuvant was used to induce AA in rats. The arthritis index (AI) was scored, and X-ray check of the hind limbs and histopathological examination were performed. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the inflamed paw tissues were measured. The administration of CAI significantly decreased the AI, restored the body weights, and ameliorated the radiological and histopathological features of joint destruction in AA rats (P<0.05, P<0.01). In addition, CAI reduced the TNF-α, IL-1β, and IL-6 levels in the inflamed paw tissues (P<0.05, P<0.01). CAI has therapeutic effect on AA rats, which may be achieved by decreasing the pro-inflammatory cytokines at the site of inflammation.