Objective To explore the effect of low-frequency stimulation( LFS) on epilepsy and its possible mechanism. Methods A total of 60 SD rats were randomly divided into control group, epilepsy model group, sham stimulation group and LFS treatment group, with 15 rats in each group. A rat model of epilepsy was established by the method of lithium chloride and pilocarpine. The Racine score and electroencephalogram of rats were recorded. Morris water maze test was used to detect the spatial learning and memory ability of the rats; Hematoxylin eosin( HE) staining and Nissl staining were used to detect the pathological changes in the hippocampus CA1 area of the rats; TdT mediated dUTP nick end labeling( TUNEL) staining was used to detect the apoptosis of hippocampal neurons; Western blot was used to detect the expression of RhoA, ROCK1, ROCK2, autophagy and apoptosis-related proteins in the hippocampus of the rats; Reverse Transcription- Polymerase Chain Reaction( RT-PCR) was used to detect the mRNA expression of RhoA, ROCK1 and ROCK2 in the hippocampus of the rats. Rusults Compared with the control group, rats in the epilepsy model group showed continuous spikes, Racine score( 4.23±0.29), escape latency[ (49.36±4.69)s], neuronal cell apoptosis rate[ (27.52±2.95)%], expression of B-lymphoma-2( Bcl-2) related X[ Bax,(0.82±0.07)], c-caspase3 (1.70±0.15), microtubule-associated proteins 1A/1B light chain 3B Ⅱ /microtubule-associated proteins 1A/1B light chain 3BⅠ[LC3Ⅱ/LC3Ⅰ,(5.20±0.42)] and Beclin1( 0.73±0.05) protein were significantly increased (all P<0.05). Expression of RhoA, ROCK1 and ROCK2 mRNA and protein were significantly increased( all P < 0.05). Swimming distance[ (240.68±22.91)cm], platform residence time[ (39.89±2.20)s], number of neurons( 17.13±3.14), number of Nissl bodies( 6.75±1.09), protein expression of Bcl-2( 0.24±0.02) and p62 (0.20±0.02) were significantly reduced( P<0.05); Compared with the sham stimulation group, the wave peak of the rats in the LFS treatment group was significantly decreased, Racine score( 2.82±0.23), escape latency [(34.83±3.85)s], neuronal cell apoptosis rate[ (9.25±0.91)%], expression of Bax( 0.43±0.05), c-caspase3 (0.53±0.02), LC3 Ⅱ/LC3 Ⅰ(1.17± 0.11) and Beclin1( 0.36±0.02) protein were significantly reduced( P< 0.05). Expression of RhoA, ROCK1 and ROCK2 mRNA and protein were significantly reduced( P < 0.05). Swimming distance[ (284.21±22.36) cm], platform residence time[ (46.85±2.93)s], the number of neurons (47.00±5.07), the number of Nissl bodies( 33.75±2.90), protein expression of Bcl-2( 0.87±0.07) and p62 (0.96±0.05) increased significantly( P< 0.05). Conclusions LFS may regulate autophagy by inhibiting the Rho/ROCK pathway to play an anti-epileptic effect.