Objective To detect changes in expression of repressor element silencing transcription factor (REST) in rapid amygdala kindling epilepsy rats. Methods Adult Sprague-Dawley rats were randomly divided into a sham group (group S), epilepsy 2 h group (group EP-2 h), epilepsy 14 d group (group EP-14 d), and epilepsy 35 d group (group EP-35 d). An experimental epilepsy kindling model of the amygdala was established by electrical stimulation. After 2 h, 14 d, and 35 d, rats were perfused and their brains were fixed and frozen for coronal sections. Immunohistochemistry was used to detect expression of REST and the neuron specific nuclear protein, NeuN. Results Expression of REST was significantly increased in the CA1, CA3, and dentate gyrus regions in groups EP compared with group S ( P < 0.05), particularly in group EP-2 h. In contrast, NeuN staining was significantly decreased in groups EP compared with group S. Visible neuronal loss was observed in the hippocampus of the EP-35 d group. Conclusions Up-regulation of REST in rat hippocampus may be involved in epileptogenesis.