In heatstroke related symptoms in streptozotocin-induced diabetic rats (STZ-diabetic rats) exposed to a high temperature (43 o C) for 60 min, like that in normal rats, the high colon temperature and the decreases of mean arterial pressure, heart rate and cerebral blood flow were abolished by MK-801, the NMDA receptor antagonist. Also, striatal glutamate was markedly released in both animals by this exposure while the release was higher and the survival time was shorter in STZ-diabetic rats than in normal rats. After insulin treatment, like that by MK-801 pretreatment, the striatal glutamate and the incidence of heatstroke in STZ-diabetic rats were markedly reduced. Therefore, heatstroke was more easily induced via the elevated striatal glutamate in STZ-diabetic rats by high temperature exposure. Insulin treatment seems helpful in the prevention of heatstroke in STZ-diabetic rats.