Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that the clinical manifestation, pathological characteristics and electroencephalography in the rat model of lithium-pilocarpine-induced mesial temporal lobe epilepsy were consistent with clinical reports of mesial temporal lobe epilepsy in humans.Immunohistochemistry staining demonstrated that P-glycoprotein positive staining was found in neurons in the pyramidal layer of the hippocampus. Westem blot assay and real-time polymerase chain reaction revealed that P-glycoprotein overexpression was exhibited in the CA1, CA3, and dentate gyrus of the hippocampus at 24 and 60 days following model induction, but no significant dffierence was detected in the same region at various time points. These results indicate that seizures led to overexpression of P-glycoprotein in neurons of the hippocampus, but no evidence was found for a positive association between P-glycoprotein expression and seizure frequency.