Objective   To observe the effect of electric stimulation on nuclear factor-κB (NF-κB)/ NOD-like receptor protein 3 (NLRP3) signaling pathway and microglial cell morphology in mice with lipopolysaccharide（LPS）induced chronic neuroinflammation, and to explore the protective mechanism of electric stimulation on brain of mice.  Methods   C57BL/6 mice were randomly divided into blank control group (n=8), model group (n=12), sham electroacupuncture group (n=6) and electroacupuncture group (n=6). Except blank control group, mice in other groups were injected intraperitoneally with LPS (0.25mg/kg) for 7 consecutive days. On the 8th day, mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days. The mice were weighed before the experiment, on the 7th and 14th days. On the 13th day, the elevated cross maze test was performed on the mice. The open field test was performed on the 14th day. After the experiment, immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1) in prefrontal cortex region. The mRNA expression of NF-κB, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), Caspase-1 and interleukin (IL)-18 were detected by Real-time PCR. The protein expression levels of NF-κB, iNOS, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, IL-1β and IL-18 were detected by Western blotting.  Results   Weight change, On the 7th day, compared with the control group, the body weight of mice in model group, sham electroacupuncture group and electroacupuncture group decreased (P<0.0001), respectively; On the 14th day, compared with the control group, the weight of mice in the model group decreased (P<0.0001); Compared with the sham electroacupuncture group, the body weight of mice in the electroacupuncture group increased (P<0.05). Elevated cross maze experiment, compared with the control group, the total distance and open arm retention time of mice in model group decreased, while the closed arm retention time increased (P<0.05). The open field experiment showed that compared with the control group, the model group mice showed a decrease in total distance traveled, slower movement speed, and fewer entries into the central area(P<0.001); Compared with the model group, the electroacupuncture group showed an increase in all three indicators(P<0.01); Compared with the sham electroacupuncture group, the total distance and motion speed of mice in electroacupuncture group both increased (P<0.05). Immunofluorescence assay, compared with the control group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased (P<0.05). Compared with the model and sham electroacupuncture group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased (P<0.05). Real-time PCR showed that compared with the control group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in the model group increased (P<0.05); Compared with the model group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in electroacupuncture group decreased (P<0.05). Western blotting indicated that compared with the control group, the protein expressions of NF-κB, iNOS, Caspase-1, IL-1β and IL-18 in model group increased (P<0.05); Compared with model group, the protein expressions of NF-κB, iNOS, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in electroacupuncture group decreased (P<0.05); Compared with the sham electroacupuncture group, IL-18 protein in electroacupuncture group decreased (P<0.05).  Conclusion   Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice, which may play an anti-inflammatory and protective role by regulating NF-κB/ NLRP3 pathway.