Adiponectin has been shown to exert insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties in metabolic diseases. It has been suggested that adiponectin may play a role in rheumatoid arthritis (RA). To assess adiponectin in serum and synovial fluid from patients with RA and osteoarthritis (OA), and in serum from healthy controls. Adiponectin and CRP levels were analyzed by ELISA. The clinical activity of RA patients was assessed according to the 28 joint count Disease Activity Score. Synovial fluid adiponectin was significantly higher in RA than in OA patients (p<0.001). Adiponectin was negatively associated with the leukocyte count in RA synovial fluid (r=-0.45, p<0.05). Serum adiponectin was higher in RA compared to healthy controls (p<0.02), however comparable to OA patients. Serum adiponectin was higher than in synovial fluid in both diseases (p<0.001). In general, women had higher adiponectin levels than men. Adiponectin was not related to age, disease duration, body mass index, or disease activity of RA patients. Adiponectin is decreased in synovial fluid compared to serum indicating that peripheral fat stores are major producers of adiponectin into the blood stream. However, increased synovial fluid adiponectin in RA patients may counterpart the local inflammatory process.