Aim: Uncoupling protein 2 (UCP2) is a member of the mitochondrial carrier superfamily. It is expressed in an impressive array of tissue. Recent studies have suggested that UCP2 can negatively control reactive oxygen species (ROS) production. The aim of the study was to assess the frequency of UCP2 gene polymorphisms in Turkish patients with epilepsy and ethnically matched healthy controls. Methods: The allelic freqency of the UCP2 gene polymorphisms were determined in subjects with epilepsy and non-epileptic healty controls. DNA samples were obtained from 60 patients and controls. Genotype of the UCP2 gene polymorphisms was determined by traditional polymerase chain reaction (PCR). Results: The distrubition of UCP2 ins/del genotypes as well as allele frequency was significantly different between epilepsy patients and controls. The prevalance of the deletion allele were 73.3% among epilepsy patients and 60.8% in the control group. In contrast, no difference was found between epilepsy patients and controls to promoter and Ala55Val polymorphisms of the UCP2 gene. We did not find any association between the exon-8 ins/del allele frequency and response to the treatment and prognosis of the patients. Discussion: To our knowlodge, this is the first study demonstrating an increase in the frequency of the exon-8 deletion allele in the UCP2 at patients with epilepsy compared to normal healthy controls. We believe that deletion of the allele might contribute to the emergence of seizure in the epileptic patients via increasing the amount of the intracellular ROS and leading to disfunction in the calcium influx.