It is well known that in diabetes mellitus the early phase insulin release response to glucose becomes blunted. Besides, autonomic neuropathy develops frequently. The autonomic nerve function is related to insulin release in normal subjects. Therefore, in the present study the autonomic function was investigated in different degrees of the early phase insulin release response to glucose loading in borderline diabetes mellitus (B-DM) as well as the early stage of diabetes mellitus (E-DM). In our study the pupillary light reflex seemed to be more sensitive for the detection of autonomic neuropathy than the cardiac beat-to-beat variation in B-DM and E-DM. The light reflex, therefore, was used and the following results were obtained. (1) Autonomic neuropathy was detected even in B-DM, though it was slighter than in E-DM. (2) The parasympathetic nerve appeared to be impaired more than the sympathetic in B-DM and this was especially the case in subjects with relatively good insulin release response. Therefore, the suppression of the early phase insulin release in B-DM may be caused by this autonomic neuropathy already present. (3) In B-DM with reduced insulin release autonomic neuropathy seemed to be more advanced and it became more remarkable in E-DM. Particularly the sympathetic abnormality was loaded in this regard. These observations suggest that it is necessary to consider an involvement of autonomic nerve dysfunction for the understanding of the pathogenesis of B-DM.