Methyl CpG binding protein-2 (MeCP2) is a multifunctional nuclear protein, and regulates dendritic morphology, synaptic transmission, spontaneous neurotransmission, and short-term synaptic plasticity in the central nervous system. This study was designed to investigate the expression of MeCP2 mRNA and protein in intractable temporal lobe epilepsy (TLE) patients and an experimental animal model. MeCP2 expression was detected in 35 temporal neocortex tissue samples from patients with intractable TLE and 14 histologically normal temporal lobe tissue samples from trauma patients without epilepsy by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and double-label immunofluorescence. In addition, the timing of MeCP2 expression was evaluated in the hippocampus and adjacent cortex of lithium chloride/pilocarpine-induced TLE rats and uninduced controls. MeCP2 was found to be expressed mainly in the nuclei of neurons, and not expressed in astrocytes. MeCP2 expression was significantly higher in the TLE patients and rats than in the control groups. Following seizures in the rat model, MeCP2 expression gradually increased in the hippocampus and adjacent cortex during the acute period (days 1 and 2) and the latent period (days 7 and 14), but decreased during the chronic period (days 30 and 60). Up-regulated expression of MeCP2 in intractable TLE patients and experimental animals suggested that MeCP2 may be involved in the pathogenesis of TLE.