Objective:To observe the effect of electroacupuncture on depression in chronic pain mice; To explore its mechanism.Methods:36 C57BL/6J mice were divided into a blank control group, a sham-operation group, a model group, and an electroacupuncture group using a random number table method, with 9 mice in each group. The chronic compression injury model of sciatic nerve was established in the model group and electroacupuncture group. Mechanical pain threshold (MWT) and latent heat wave leg reflex (TWL) were measured on preoperative day 1 and postoperative days 4, 7, 14, 21, and 35. Electroacupuncture treatment was performed on the 14th day after modeling, and on the 35th day after modeling, open field experiments, elevated cross maze experiments, forced swimming experiments, and tail suspension experiments were conducted to evaluate depressive like behavior in mice. Western blot was used to detect the protein expressions of glutamate receptor 1 (GluA1), glutamate receptor 2 (GluA2), human glucose transporter 3 (GLUT3), and calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in the hippocampus of each group of mice; GluA1 positive cells in the hippocampus of mice was observed using immunofluorescence technology.Results:Compared with the blank group, the MWT and TWL value of the model group decreased ( P<0.05) on postoperative days 4, 7, 14, and 21. Compared with the model group, the electroacupuncture group had a longer stay time in the central area of the open field ( P<0.01), an increased percentage of stay time and activity frequency in the elevated arm opening ( P<0.01), a shorter static time for forced swimming ( P<0.01), and a shorter immobility time for the suspended tail ( P<0.01). Compared with the model group, the expressions of GluA1, GLUT3, GluA2, and CaMKⅡ proteins in the hippocampus of mice in the electroacupuncture group increased ( P<0.05), and the number of GluA1 positive cells increased ( P<0.05). Conclusion:Electroacupuncture can affect synaptic plasticity by regulating the AMPA receptor in the hippocampal region, thereby improving depressive mood caused by chronic pain.