Previous papers showed that people with diabetes mellitus have higher prevalence of mental disorders than healthy people. This difference may be linked to impaired social interaction, though it is yet not clear how diabetes impairs social interaction. In the present study, we investigated the role of neuropeptide Y (NPY) and glutamatergic functions in impairment of social interaction in streptozotocin (STZ)-induced diabetic mice. In social interaction test, interaction time with the stranger mouse was decreased in STZ-induced diabetic mice. NPY mRNA level in the hypothalamus was increased in STZ-induced diabetic mice. Intracerebroventricular (i.c.v.) injections of both NPY Y₂ (NPY 13-36) and AMPA (AMPA) receptor agonists decreased interaction time with the stranger mouse in non-diabetic mice, which was inhibited by respective antagonists BIIE 0246 and NBQX. In addition, decrease in interaction time with the stranger mouse induced by i.c.v. injection of NPY 13-36 was blocked by NBQX. Moreover, injections of both BIIE 0246 and NBQX into the basolateral amygdala, an important brain area in social behavior, reversed the decrease in interaction time with the stranger mouse in STZ-induced diabetic mice. These results suggest that amygdalar NPY and glutamatergic functions are altered in diabetes, which impairs social interaction.