Background and Objectives: Rheumatoid arthritis (RA) is an inflammatory disease treated with nonsteroidal anti-inflammatory drugs that have different side effects. One of the plants used for this purpose in the traditional medicine is Trachyspermum ammi. The present study aimed at investigating the anti-inflammatory effect of this plant on type II collagen-induced arthritis (CIA) in Wistar rats. Materials and Methods: The study was performed on 35 male Wistar rats. Seven rats were considered as the healthy control group (normal group), and CIA was stablished in the rest. The rats with a model of inflammatory arthritis were divided into four groups. One group did not receive any treatment and three groups were treated orally with ibuprofen (15 mg/kg), aqueous extract of the T. ammi seeds (100 mg/kg), or their combination for 30 days. The effect of different treatments was investigated on the paw thickness, arthritis score, and mRNA level of COX2 and iNOS genes. Results: CIA increased paw thickness, arthritis score, and COX2 and iNOS mRNA levels compared to those of the normal group. Treatment with ibuprofen and aqueous extract alone or in combination reduced the studied variables. Reduction in the paw thickness, arthritis score, and iNOS mRNA level was more in the ibuprofen-treated group than the T. ammi extract-treated group, but treatment with T. ammi extract reduced COX2 mRNA level more than ibuprofen. Conclusion: It seems that the aqueous extract of T. ammi can be used alone or in combination with ibuprofen to treat RA.