Objective To investigate the expression of glutathione S-transferase π (Glutathione S-transferase π, GST-π) protein in peripheral blood and brain of patients with drug-resistant epilepsy and refractory epilepsy rats. Meth?ods From January 2010 to March 2014, the expression of GST-πin the blood and brain of 32 cases of drug-resistant epi?lepsy underwent neurosurgery and 10 cases of cerebral vascular malformation underwent surgery were studied and com?pared. The expression of GST-πin the blood and brain in refractory epilepsy rats and normal rats were studied and com?pared. Results The specimen from 20 temporal, 6 frontal and 6 occipital lobes were obtained from drug-resistant epilep?sy patients. The expression levels of GST-πin the blood and brain in refractory epilepsy rats and normal rats were higher than those of the control groups (P<0.05). Conclusion GST-πmay be involved in the process of drug-resistant epilepsy. The GST-πexpression in blood may be used as a marker for resistance to anti-epileptic agents.