To determine whether erythrocyte sorbitol content could become an indicator of diabetic microangiopathy, we studied the relationship between the changes in erythrocyte sorbitol content in response to diet loading and diabetic microangiopathy in patients with non-insulin-dependent diabetes mellitus. The increase of change in erythrocyte sorbitol content (delta Sor) after diet loading (420 kcal) significantly correlated with that of plasma glucose levels (delta BS). The patients with less than or equal to 40 m/s of motor or sensory nerve conduction velocity (MCV and SCV) had significantly higher delta Sor and delta Sor/delta BS values than those with greater than 40 m/s of MCV and SCV; nevertheless, there were no significant differences in delta BS between the two groups. Furthermore there was a significant negative correlation between nerve conduction velocity and delta Sor and Delta Sor/delta BS values. On the other hand, the patients with nephropathy or retinopathy showed no significant increase in delta Sor or delta Sor/delta BS compared with patients without these complications. The results demonstrated that delta Sor and delta Sor/delta BS could become indicators of the presence or severity of diabetic neuropathy. Furthermore the more significant participation of alteration in the polyol pathway in the pathogenesis of neuropathy than of the other microangiopathies was suggested.