Resistin is a newly identified adipocytokine, which has demostrated links between obesity and insulin resistance in rodents. In humans, pro-inflammatory properties of resistin are superior to its insulin resistance-inducing effects. To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis (RA), osteoarthritis (OA) and spondylarthropaties (SpA), and to study its relationship to inflammatory status and RA disease activity. Resistin expression and localization in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, IL-1 beta;, IL-6, IL-8, TNF-alfa;, and MCP-1 levels were measured. The clinical activity of RA patients was assessed according to the 28 joint count Disease Activity Score (DAS28). Resistin was detected in both RA and OA synovium. Staining in the sublining layer was more intensive in RA compared to OA patients. In RA macrophages (CD68+), B-lymphocytes (CD20+), and plasma cells (CD138+), but not T- lymphocytes (CD3+) showed co-localization with resistin. Synovial fluid resistin was higher in RA than in SpA or OA patients (both p<0.001). In patients with RA and SpA, serum resistin levels were higher compared to those in patients with OA (p<0.01). Increased serum resistin in RA patients correlated with both CRP (r=0.53, p<0.02), DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. The up-regulated resistin at local sites of inflammation and the link between serum resistin, inflammation, and disease activity suggest a role for resistin in the pathogenesis of RA.