The present studies were designed to determine whether streptozotocin-induced (STZ-induced) diabetes in mice can attenuate the development of antinociception induced by exposure to both foot shock and forced swimming stress. Foot shock stress produced significant analgesia both in control and diabetic mice. However, the extent of foot shock stress-induced analgesia (FSSIA) in diabetic mice was significantly lower than that in control mice. Naloxone (2 mg/kg, i.p.) significantly attenuated FSSIA in control mice, but was without effect on FSSIA in diabetic mice. One-minute swimming stress had no significant effect on tail-pinch latency in control mice, whereas 3-min swimming stress produced significant analgesia in these mice. Diabetic mice exhibited robust swimming stress-induced analgesia (SSIA): one-min swimming stress produced significant analgesia in diabetic mice. These analgesic effects were blocked by naltrindole, a selective antagonist of delta-opioid receptors, but not by pretreatment with beta-funaltrexamine, an irreversible and selective antagonist of mu-opioid receptors. These results suggest that the deficiency in the functioning of mu-opioid receptors caused by diabetes results in significant activation of an endogenous analgesic system, which is mediated mainly by delta-opioid receptors.