Background/Aim: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. Methods: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. Results: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 ± 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 ± 0.6 pg/ml in patients with microalbuminuria and then to 4.4 ± 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. Conclusion: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.