It is thought that diabetes mellitus causes increased polyol pathway activity and decreased tissue myo-inositol levels. We analyzed myo-inositol contents in red blood cells from normal and diabetic subjects by high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD) which is a sensitive and simple method. The RBC myo-inositol levels were 91.58±27.45 (mean±SD) nmol/gHb in the normal subjects (n=24), 151.71±53.16nmol/gHb in diabetic subjects without microangiopathy (n=41), and 253.64±79.10nmol/gHb in diabetic sublects with microangiopathy (n=14). Concentrations of RBC myo-inositol in diabetic subjects without microangiopathy were significantly higher than those in normal individuals (P<0.01). Moreover, a significant increase in myo-inositol levels was observed in diabetic patients who had microangiopathy, as compared to those without microangiopathy, in all examined samples (P<0.01) incl ding glucose-or HbA1c-matched samples (P=0.0018). Although it is well known that RBC myo-inositol is increased in patients with renal failure, we found that concentrations of RBC myo-inositol in diabetic subjects (170.32±63.42nmol/gHb, n=39) were still significantly higher than those in normal individuals (P<0.01) even with a normal serum creatinine level. On the basis of these results, we suggest that determination of RBC myo-inositol by the HPLC-PAD method is useful for evaluating diabetic microangiopathy.