Objective To investigate the transcriptomic characteristics of epilepsy and explore potential targets for the diagnosis and treatment of epilepsy.Methods A total of 17 young male Sprague-Dawley rats were randomly divided intocontrol group （n=8） and chronic spontaneous recurrent seizures （CSRS） group （n=9）. Lithium chloride-pilocarpine was used to establish a rat CSRS model. Transcriptome sequencing （RNA-seq） was performed on the rat hippocampal tissues from the CSRS and control groups. A differential analysis and a signaling pathway enrichment analysis on messenger RNA （mRNA） and microRNA （miRNA） were performed， and a differentially expressed protein-protein interaction network was constructed to search for core regulatory genes.Results A total of 354 differentially expressed genes （DEGs） were obtained via the differential analysis on mRNA between the control group and the CSRS group. The signaling pathway enrichment analysis showed that DEGs were related to ion transport regulation， tissue development， stress response， etc. The protein-protein interaction network analysis revealed that WDR88， SHANK2， TEC， NFKBIZ， EPHA8， etc.， were the main core regulatory genes in DEGs. In addition， differentially expressed miRNA was obtained. Target genes were predicted， and the GO pathway was enriched. It was found that the target genes were mainly related to the molecular functions such as ionic glutamate receptor complex， glutamate receptor activity， glutamate-dependent calcium channel activity， and NF-κB-inducing kinase activity.Conclusions Based on the results of RNA-seq， it was found that abnormal expression of differentially expressed genes is an important cause of epilepsy， and it is a key factor leading to abnormal and synchronized discharge of neurons.