The role of opioid receptors in diabetes and hyperglycemia-induced analgesia was studied in male Sprague-Dawley rats. Animals maintained under controlled environmental conditions were used in all studies. Pain latency was determined by the hot plate test (55 degrees C) and analgesy-meter force method. The results of these studies indicate that streptozotocin-induced diabetic animals have a significantly higher pain threshold (P less than 0.01) than the control groups. The pain threshold was found to be diurnally controlled with a peak at the beginning of the light phase (1000 hours) and a trough at the end of the dark phase (0800 hours). Diabetes-induced analgesia was found to be reversed by both acute or chronic insulin administration. In another study, glucose-induced hyperglycemic rats were found to have a significantly higher pain threshold (P less than 0.01) than control animals, with a peak occurring at the beginning of the dark phase (2000 hours), and a trough at the beginning of the light phase (0800 hours). The administration of the opioid antagonist naloxone (2 mg/kg) reversed the hyperglycemia and diabetic-induced analgesia. The results of these studies might indicate that analgesia found in diabetic or hyperglycemic animals may be related to the endogenous opioid system.