To clarify the influence of blood glucose level or diabetes mellitus on serum KL-6, a mucin-like glycoprotein, concentrations, they were measured against 176 diabetic subjects, including receiving insulin (INS) group (n=54), oral antidiabetics (OAD) group (n=78), and diet and exercise (D&E) group (n=44). Serum KL-6 concentrations in the diabetic subjects were significantly greater than those in the normal healthy control subjects (643.0+/-32.7 U/ml, 206.5+/-6.1 U/ml, P<.0001, respectively), and those in the INS and OAD groups were significantly greater than those in the D&E group (708.2+/-66.9, 691.7+/-51.9, and 476.6+/-34.9 U/ml, P<.05, P<.05, respectively). Serum KL-6 concentrations did not correlate with urine KL-6 concentrations (n=73, r= -.044, P= .74). Immunohistochemical staining of the diabetic kidneys with a monoclonal antibody to KL-6 antigen showed positive immunoreactivity on Henle's loop, renal tubules, and epithelial cells in Bowman's space of sclerosing glomerulus. In conclusion, diabetes mellitus or complications of diabetes mellitus resulted in serum KL-6 elevation regardless of serum glucose level, but serum KL-6 concentrations were not influenced despite control of diabetes mellitus.