Background— Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature atherosclerosis is the major cause of morbidity and mortality in type 2 diabetes. Here, we report the identification of a soluble form of CD36 (sCD36) in plasma and hypothesize that sCD36 would be elevated in patients with type 2 diabetes and insulin resistance. Methods and Results— sCD36 in plasma was demonstrated by immunopurification and Western blotting. We established ELISA assays to determine sCD36 in plasma and measured sCD36 in obese type 2 diabetic patients, obese nondiabetic relatives, and obese and lean control subjects. sCD36 was markedly elevated in type 2 diabetic patients compared with both lean (5-fold) and obese (2- to 3-fold) control subjects. There was a strong, inverse correlation between sCD36 and insulin-stimulated glucose disposal and a direct correlation with fasting plasma glucose, fasting insulin, and body mass index. Conclusions— Our study demonstrates sCD36 in plasma for the first time. sCD36 is highly related to risk factors of accelerated atherosclerosis in type 2 diabetes such as insulin resistance and glycemic control, and we propose that sCD36 might represent a marker of the metabolic syndrome and a potential surrogate marker of atherosclerosis.