Objective: To study the neurochemical change during high-frequency stimulation of the subthalamic nucleus in epileptic rats. Methods: Two animal groups -12 rats with epilepsy induced by the systemic administration of kainic acid and 12 normal rats - were used. Concentric bipolar electrodes were stereotaxically implanted in the unilateral subthalamic nucleus (STN), stimulated by high frequencies of 130 and 260 Hz in each group. The microdialysis probes were unilaterally lowered into the globus pallidus (GP) and the substantia nigra pars reticulata (SNr). The concentrations of glutamate (Glu) and gamma-aminobutyric acid (GABA) in dialysate samples were determined by high-performance liquid chromatography. Results: Electrical stimulation of the STN induced increases in GABA content in the SNr of each group, while GABA remained stable in the GP. The extracellular GABA level in the epileptic group was significantly higher than that of the normal group. In addition, the frequency of 130 Hz provoked the maximum increase in Glu contents both in the GP and SNr, whereas 260 Hz had less effect. Conclusions: This study demonstrates the neurochemical modifications in STN targets during electrical STN stimulation and shows that different frequencies of high-frequency stimulation have different effects on the neurotransmitters.