Objective To investigate the regulation mechanism of microglia activation, and learning and memory function, by electroacupuncture of the subgranular area of the dentate gyrus (SGZ) of depressed rats. Methods SD rats were randomly divided into four groups: the control group, model group, NLRP3 blocker group, and electroacupuncture group. The rat depression model was established by orphan rearing and chronic unpredictable gentle stimulation. The electroacupuncture group was administered electroacupuncture stimulation at the “Baihui” and “Yintang” acupoints for 20 min / d. The NLRP3 blocker group was injected with MCC950 solution (3 mg / kg) through the tail vein for 21 days. An open field experiment was used to record the autonomous activity of animals before and after modeling. The Morris water maze test was used to detect learning and memory function, and the immunofluorescence double-staining method was used to quantify and locate the protein expression of SGZ microglia marker Iba-1 and inflammasome Nod-like receptor 3. The relative expression levels of Caspase-1 and interleukin-1β in the SGZ were detected by real-time quantitative PCR. Results Compared with the control group, autonomous activity and learning and memory function were significantly reduced, the activation of SGZ microglia was obvious, the positive detection of NLRP3 protein was significantly increased, and the relative expression levels of Caspase-1 and IL-1β protein were also increased in the model group (P< 0. 01). Compared with the model group, the electroacupuncture group and the NLRP3 blocker group showed significantly improved autonomous activity and learning and memory function, and decreased positive detection rates of NLRP3+IBA-1 protein expression and relative expression of Caspase-1 mRNA ( P< 0.05, P< 0.01 ) and IL-1β mRNA. Conclusions Electroacupuncture improved the learning and memory ability of depressed rats, which may be related to the regulation of the activation state of microglia and the NLRP3 / caspase-1 signaling pathway in the subgranular area of the hippocampus.