@@ The long-term application of opioids can reduce the effectiveness of opioid analgesic and contradictorily cause hyperalgesia, then tolerance phenomenon occurs (opioid tolerance), this is the important reason of the limitation of opioid clinical use. Recent studies have shown that excitatory amino acid receptors, such as N-methyl-D-aspartate receptor (NMDAR) involved with the occurrence of chronic opioid tolerance and associated abnormal pain sensitivity. NMDAR activation can cause neurotoxicity in a variety of circumstances, resulting in apoptosis [1] .Glutamate is the synaptic NMDAR endogenous ligands and the stability of the level of extracellular glutamate is strictly regulated by glutamate transporters (glutamate transporter, GT).The level of excitatory amino acids such as glutamate increase and the activation of excitatory amino acid receptors such as NMDAR play an important role in the occurrence of abnormal pain sensitivity. Therefore, this study will investigate the effect of NMDAR and glutamate transporter on the mechanism of morphine tolerance development, and to elucidate the implication of neuronal apoptosis of spinal dorsal horn in chronic morphine tolerance.