OBJECTIVE: To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats. METHODS: Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses. RESULTS: The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats. CONCLUSION: This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.