To identify protein biomarkers linking to disease activity and treatment responses of patients with rheumatoid arthritis (RA), proteomic study using mass spectrometric analysis of plasma proteins was performed. Proteomic profiling technologies can simultaneously resolve and analyze multiple proteins in plasma. Evaluation of multiple proteins of the plasma will be essential to discover protein biomarkers. In this study, we used protein chip surface enhanced laser desorption/ionization time of flight mass spectrometry approach (SELDI-TOF MS). Through differential profiling of plasma proteins, we selected two prospective candidate biomarkers. One mass spectrometric peak distinguished patients with RA from healthy controls was transthyretin (TTR) and the other distinguished inactive patients with RA from patients with active RA was Serum Amyloid A (SAA). This study demonstrates that proteomic profiling using mass spectrometry of plasma greatly facilitates global discovery and verify clinically relevant sets of disease biomarker directly links to disease activity and treatment responses.