Rheumatoid Arthritis (RA) is a chronic inflammatory disorder of the synovial membrane that results in the destruction of bone and cartilage in affected joints. In order to identify novel disease-related proteins and candidate biomarkers, we analyzed the changes in the serum proteome profiles of rats with RA that were treated with a COX-2 inhibitor, celecoxib and a DMARD, methotrexate. Serum samples were collected from the RA rats before and after the drug treatment. Following immunodepletion of major proteins, the proteins were digested. The proteins were identified using MALDI-TOF mass spectrometry. Several proteins are identified and the proteins that play a key role in RA are studied. These proteins are inhibited differentially by celecoxib and methotrexate. Although some of the proteins are known to be related to RA, several are currently unknown with respect to their relationship to RA and may be involved in the development of this disease. Our results may contribute to the identification of novel disease related proteins and enhance the understanding of the pathogenesis of RA.