The analgesic potency of morphine degrades rapidly after repeated administration, which is known as morphine antinociceptive tolerance. Series of progress have been made towards illustrating the mechanisms underlying morphine antinociceptive tolerance, but the details still remains unknown. Most of the researches in the past years prevailingly focused on neuronal mechanisms of adaptation, sensitization, and so on. Recently, much attention has been paid to investigate the critical role of glia and purinergic recepter in morphine antinociceptive tolerance. We summarize the research progress of P2X recepters in morphine antinociceptive tolerance in this review.