Objective To investigate the effect of low-frequency stimulation （LFS） on epilepsy and its possible mechanism.Methods A total of 60 Sprague-Dawley rats were randomly divided into control group （n=15）， epilepsy model group （n=15）， sham stimulation group （n=15）， and LFS treatment group （n=15）. The Racine scores and electroencephalograms of the rats were recorded. The Morris water maze test was used to test the spatial learning and memory ability of the rats； hematoxylin-eosin staining and Nissl staining were used to detect the pathological changes in the hippocampal CA1 region of the rats； TUNEL staining was used to determine the apoptosis of rat hippocampal neurons； enzyme-linked immunosorbent assay was used to measure the levels of TNF-α， IL-6， and IL-1β in rat serum； Western blot was used to determine the expression of RhoA， ROCK1， ROCK2， p65， p-p65， and apoptosis-related proteins in rat hippocampus； reverse transcription polymerase chain reaction was used to measure the expression of RhoA， ROCK1， and ROCK2 mRNA in rat hippocampus.Results Compared with the control group， the rats in the epilepsy model group showed continuous spike waves and had significantly higher Racine score， neuronal apoptosis rate， expression of Bax， c-caspase3， and p-p65/p65 proteins， as well as RhoA， ROCK1， and ROCK2 mRNA and proteins， and levels of TNF-α， IL-6， and IL-1β in serum （P<0.05）， and had significantly lower spatial learning and memory ability， number of neurons， number of Nissl bodies， and expression of Bcl-2 protein （P<0.05）. Compared with the sham stimulation group， the rats in the LFS treatment group had significantly lower wave crest， Racine score， neuronal apoptosis rate， expression of Bax， c-caspase3， and p-p65/p65 proteins， as well as RhoA， ROCK1， and ROCK2 mRNA and proteins， and levels of TNF-α， IL-6， and IL-1β in serum （P<0.05）， and had significantly higherspatial learning and memory ability， number of neurons， number of Nissl bodies， and expression of Bcl-2 protein （P<0.05）.Conclusions LFS may inhibit inflammation by inhibiting the Rho/ROCK/NF-κB pathway， thereby playing a protective role in epileptic rats.