The authors evaluated serum retinol, retinol-binding protein (RBP), and beta-carotene levels to elucidate the retinoid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). The mean retinol levels by gender (1.83 mumol/L for females and 2.24 mumol/L for males) in diabetics were higher than those (1.31 mumol/L for females and 1.82 mumol/L for males) in control subjects (P < 0.0001, P < 0.01, respectively). The mean retinol/RBP ratios (0.95 for females and 0.97 for males) of diabetics were higher than those of the control subjects (0.60 for females and 0.64 for males) and of male patients having impaired glucose tolerance (0.55) (P < 0.0001). Lipid-lowering medication significantly decreased retinol, with decreasing apolipoprotein C-II but without a commensurate decrease in RBP. The retinol levels had a positive correlation with apolipoprotein C-II in all or normolipidemic patients with diabetes and control subjects. The high retinol/RBP ratio implies that an excessive or free retinol possibly exists in NIDDM. An alternative metabolism of retinol is inferred to underlie NIDDM without direct influences of cholesterol or triglyceride themselves.