Deltorphin I is a δ-opioid receptor agonist with high affinity and selectivity. Twice daily administration of Deltorphin I (20μg/mouse) for 4 days produces tolerance to Deltorphin I analgesia, as shown by the decrease in the analgesic response. The peak analgesic response to Deltorphin I (20 μg/mouse) at 10 min after injections is decreased from 8.36±0.28 s (the 1st day) to 4.53±0.14 s (the 4th day) markedly. Concurrent treatment of Melatonin (0.5, 1 and 2.5 mg/kg) and Deltorphin I (20 μg/mouse) twice daily for 4 days can attenuate the tolerance to Deltorphin I analgesia (P<0.05, <0.05 and <0.05), and this effect is dose dependent.