Objective To explore the effect of Chaihu Shugan Decoction for the treatment of rats with epilepsy and its influence on miR⁃34a expression. Methods A total of 42 rats were randomly assigned to epilepsy group (n=15), Chaihu Shugan Decoction group (n=12), or blank group (n=15). Except for the blank group, the epilepsy rat model was established on the epilepsy group and the Chaihu Shugan Decoction group by employing the method of intraperitoneal injection of lithium chloride-pilocarpine hydrochloride. After the end of modeling, rats in the Chaihu Shugan Decoction group received intragastric administration of 2 mL/100 g Chaihu Shugan Decoction, whereas the blank group and the epilepsy group received intragastric administration of equivalent normal saline. All rats were given continuous intragastric administration once a day for 3 weeks. After the end of modeling, the microRNA microarray was used to detect miRNA of differential expression in hippocampus tissues in rats model with epilepsy. The epileptic seizure of rats in 3 groups was observed and recorded during intervention. The expression of miR-34a in hippocampus tissues of the 3 groups was detected by employing the real-time fluorescent quantitative PCR after the last time of intragastric administration. Results The analysis of MicroRNA microarray sequencing revealed that a total of 40 miRNAs of differential expression were screened out from hippocampus tissues in rats with epilepsy, therein miR-34a was high-expressed in hippocampus tissues of rats model with epilepsy. Compared with the epilepsy group, the Chaihu Shugan Decoction group exhibited decreased frequency of epileptic seizure, and shorter seizure duration (P<0.05). Compared with the blank group, the epilepsy group and the Chaihu Shugan Decoction group yielded elevated miR-34a expression in hippocampus tissues of rats model (P<0.05). Compared with the epilepsy group, the Chaihu Shugan Decoction group interpreted decreased miR-34a expression in hippocampus tissues of rats model (P<0.05). Conclusion Chaihu Shugan Decoction may reduce epileptic seizure by inhibiting expression of miR-34a in hippocampus tissues of rats model with epilepsy.