Objective To explore the mechanism of ellagic acid (EA) in reducing epileptic seizures in rats. Methods Rats were divided into 6 groups: control group (n=12), model group (n=11), EA low dose group (n=11), EA medium dose group (n=11), EA high dose group (n=11) and agonist group (n=11). Control group was normal SD rats, and other groups were epileptic rats induced by pentylenetetrazol (PTZ) (35 mg/kg). Control group and model group were intraperitoneally injected with normal saline, while EA low dose group, EA medium dose group and EA high dose group were intraperitoneally injected with 25, 50 and 100 mg/kg/d EA, respectively. The rats in agonist group were intraperitoneally injected with EA of 100 mg/kg/d and 20 μg/kg/d recombinant rat interleukin-6 (rrIL-6). The drug was given for 4 weeks. 24 hours after the last administration, PTZ (35 mg/kg) was injected intraperitoneally again, and the latency and duration of convulsion were recorded. Hippocampal neuronal damage was observed by HE and Nissl staining. The contents of IL-6, IL-1β and tumor necrosis factor-α (TNF-α) were measured by ELISA method. The expression of glial fibrillary acidic protein (GFAP) in hippocampus was detected by immunofluorescence staining. The expressions of GFAP, phosphorylated-Janus kinase 2 (p-JAK2), JAK2, phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and STAT3 in hippocampus were detected by Western blot.Results Compared with control group, model group showed obvious convulsion, obvious neuronal damage, Nissl + neuron count decreased, hippocampus IL-6, IL-1β and TNF-α content increased, hippocampus CA1 region GFAP relative fluorescence intensity and protein relative level increased, and the relative levels of p-JAK2 and p-STAT3 proteins in hippocampus increased (P＜0.05). Compared with the model group, the convulsion latency of the EA low dose group, EA medium dose group and EA high dose group were prolonged, the duration was shortened, neuronal damage was significantly reduced, Nissl + neuron counts increased, hippocampal IL-6, IL-1β and TNF-α contents decreased, hippocampus CA1 region GFAP relative fluorescence intensity and protein relative level decreased, and the relative protein levels of hippocampal p-JAK2 and p-STAT3 decreased (P＜0.05). Compared with the EA high dose group, the convulsion latency of the agonist group was shortened, the duration was prolonged, neuronal damage was aggravated, Nissl + neuron count decreased, hippocampus IL-6, IL-1β and TNF-α content increased, hippocampus CA1 region GFAP relative fluorescence intensity and protein relative level increased, and the relative levels of p-JAK2 and p-STAT3 proteins in hippocampus increased (P＜0.05). Conclusion EA inhibits neuroinflammation and excessive activation of astrocytes by inhibiting JAK2/STAT3 signal pathway, thus reducing epileptic seizures in rats