Neuroinflammation plays a critical role in ischemic stroke pathology and could be a promising target in ischemic stroke. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor in the CNS that is involved in regulating neuroinfiammation in cerebral ischemia. However, the role of TREM2 in ischemic stroke is controversial. Electroacupuncture (EA) is an effective therapy for alleviating stroke-induced neuroinflammation. Here, we found that ischemic stroke induced an increased microglial TREM2 expression, and EA treatment can further promote microglial TREM2 expression following cerebral ischemia. TREM2 overexpression was observed to play a neuroprotective role by improving the neurobehavioral deficit and reducing the cerebral infarct volume 72 h after reperfusion, whereas TREM2 silencing had the opposite effects. Moreover, the effects of EA on improving stroke outcome and suppressing neuroinfiammation in the brain were reversed by TREM2 silencing. Finally, TREM2 silencing also suppressed the ability of EA to regulate the PI3K/Akt and NF-kappa B signaling pathways. Altogether, the results show that TREM2 could be a potential target in EA treatment for attenuating inflammatory injury following cerebral ischemia/reperfusion. (C) 2018 Elsevier Inc. All rights reserved.