To explore the effect of NLRP3 on the hippocampal dentate gyrus in the pilocarpine-induced rat epilepsy model. Methods: Twelve rats were randomly selected from 64 adult SD rats as controls, and the others were induced by lithium-pilocarpine to create the epilepsy model. After model establishment, the rats were randomly divided into the 1 d, 7 d, 14 d, and 28 d groups (n=12 per group). The serum levels of IL-1β and TNF were detected with ELISA. The expression of NLRP3 and Caspase-1 in the hippocampal dentate gyrus was measured with immunohistochemistry and RT-PCR. Results: The serum levels of IL-1β and TNF in the 7 d, 14 d, and 28 d group rats were higher than those in control group rats (P<0.01), and that of the 28 d group was highest among all groups (P<0.01). The average optical density and mRNA expression of NLRP3 and Caspase-1 in the hippocampal dentate gyrus of 7 d, 14 d, and 28 d group rats were higher than those in control group rats (P<0.01), and that of the 28 d group was highest among all groups (P<0.01). Conclusion: Expression of NLRP3 and Caspase-1 increased in the hippocampal dentate gyrus of pilocarpine-induced model rats during the progression of chronic spontaneous epilepsy. This may be associated with activation of the inflammatory response.