Abstract: Purpose: The pathogenesis of Rheumatoid Arthritis (RA) is not well understood. Looking for three mediators [Soluble Interleukine 2 Receptor (SIL2R), ß2 Microglobulin (ß2M) and Tumor Necrosis Factor α (TNF α)] in RA patients sera and synovial fluid (SF) may clear some aspects of it. Methods: The above named mediators were estimated in 72 RA patient sera and SF, 13 patient with osteoarthritis (as patient control) and 130 blood donor (as normal control). Samples have been take at active phase of disease. ELISA technique was employed to evaluate them. Results: Significant difference was observed between RA patients and two control groups (P<0.001). Total amount of SIL2R,ß2M and TNF α showed a higher concentration in patient synovial fluid than sera. There was a positive relation between the level of mediators and the active phase of RA. Conclusion: These results indicate that local synthesis of SIL2R, ß2M and TNF α might be the cause of higher level presence of them in SF. It also supports the idea that these mediators have a proinflammatory action in RA and contributes the pathogenesis of joint damage in RA.