Down's syndrome (DS) is the most frequent chromosomal aberration in men. Moreover DS is considered an atheroma-free model. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-alpha high sensitivity (hsTNF-alpha), leptin and adiponectin from non-demented DS subjects of three different age cohorts (2-14, 20-50 and above 60 years) and healthy controls were measured. No clinical and sub-clinical inflammation was apparent in DS patients. Plasma levels of hsTNF-alpha, IL-6 and leptin were higher in children than in adult and old DS subjects. Instead, serum levels of adiponectin were increased in older DS patients than in DS children and adults. High levels of circulating adiponectin might protect DS from clinical complications of atherosclerosis.