Various studies proved spinal AMPA receptors were involved in the formation of neuropathic pain. In this study, we investigated the effect of methyl cinnamate (MC), a flavoring agent widely used in food and commodity industry, on CCI-induced upregulation of spinal AMPARs and pain hypersensitive behaviors. Results indicated that MC treatment dosage-dependently inhibited CCI-induced mechanical and thermal hypersensitivity. To further investigate the effect of MC after the formation of neuropathic pain, MC at the dosage of 100 mg/kg was administrated on day 7–14 on CCI rats. Results showed that MC treatment for seven days alleviated CCI-induced pain hypersensitivity after the formation of neuropathic pain. MC treatment reversed CCI-induced upregulation of GluR2, GluR3 and phosphorylation of GluR1. Further, MC dosage-dependently alleviated CCI-induced activation of mTOR and the downstream p70s6k. MC dosage-dependently induced activation of AMPK. All the MC-induced effects in CCI rats were completely reversed by Compound C, a AMPK inhibitor. These results meant MC treatment mitigated CCI-induced upregualtion of spinal AMPA receptors and pain hypersensitive behaviors through actviation of AMPK.