The effect of naloxonazine, a selective mu(1)-opioid receptor antagonist, on oxycodone-induced antinociception was examined in streptozotocin-induced diabetic mice. Oxycodone (5 mg/kg, s.c.) induced significant antinociception in both non-diabetic and diabetic mice. This antinociceptive effect of oxycodone was completely antagonized by pretreatment with naloxonazine (35 mg/kg, s.c.) in both non-diabetic and diabetic mice. The selective kappa-opioid receptor antagonist nor-binaltorphimine (20 mg/kg, s.c.) also antagonized oxycodone-induced antinociception in diabetic mice, but only had a partial effect in non-diabetic mice. These results suggest that although primarily interacts with mu(1)-opioid receptor, kappa-opioid receptors are also strongly involved in oxycodone-induced antinociception.