To investigate a role of the Maillard reaction in the pathogenesis of diabetic nephropathy, we measured serum levels of 3-deoxyglucosone (3-DG), a potent protein cross-linking intermediate of the Maillard reaction, and tissue contents of advanced glycation end products (AGEs) in streptozotocin (STZ)-induced diabetic rats. We quantified serum 3-DG using gas chromatography/ mass spectrometry, and measured AGE contents in tissues using a competitive enzyme-linked immunosorbent assay with a monoclonal anti-AGE antibody. The STZ-induced diabetic rats showed nephropathy with proteinuria, hypoproteinemia, hyperlipidemia and reduced creatinine clearance. Serum levels of 3-DG in the STZ-induced diabetic rats (mean ± SE; 3.46 ± 0.23 μmol/l) were significantly (p < 0.01) higher than those in control rats (1.23 ± 0.13 μmol/l). AGE contents in the kidney and the lens obtained from the STZ-induced diabetic rats (398 ± 45 and 816 ± 200 arbitrary units, respectively) were also significantly (p < 0.01) higher than those in the control rats (122 ± 10 and 299 ± 50 arbitrary units, respectively). The results indicate that increased levels of serum 3-DG and renal tissue AGEs may be related to the occurrence of diabetic nephropathy.