3-Deoxyglucosone, a potent protein crosslinking intermediate of the Maillard reaction, was first detected in diabetic serum using gas chromatography/mass spectrometry. Serum concentration of 3-deoxyglucosone was elevated in diabetic patients as compared with healthy subjects. More notably, diabetic patients with nephropathy showed higher serum concentration of 3-deoxyglucosone than those without nephropathy. The increased serum concentration of 3-deoxyglucosone in the diabetic patients suggests that 3-deoxyglucosone may be responsible for the development of diabetic complications such as diabetic nephropathy by promoting the formation of advanced glycation end products.