Somatostatin (SST) may protect organism from overnutrition-induced insulin resistance and oxidative stress by inhibiting pancreatic endocrine and exocrine secretion, gastrointestinal digestion and absorption. Many studies clearly show its release becomes perturbed in diabetes and obesity. Therefore, in the present study we first aimed to investigate whether or not plasma somatostatin level was different in patients with hyperlipidemia and normolipidemic controls. We also assessed the relationship between plasma somatostatin levels with atherosclerotic index (AI) and malondialdehyde (MDA) in non-diabetic dyslipidemic patients. Subjects with hyperlipidemia have insulin resistance and high levels of oxidative stress. Median somatostatin (57.2±19.2 vs 68.0±21.9 pg/mL; p<0.05) levels were lower in hyperlipidemic than in normolipidemic subjects. Significant inverse relationships between SST level and AI (r=-0.21, p< 0.05), or MDA (r=-0.31, p<0.01) were observed. These results suggest a possible protective role of endogenous SST, at least on hyperlipidemia and atherosclerosis that are attributed to excess energy intake and physical inactivity. Of course these preliminary results should be supported by prospective studies.