ObjectiveTo observe the expressions of p-mTOR, p-S6K1 and p-4EBP1 in the human brain with refractory epilepsy and to explore the role of mTOR signaling pathway in intractable epilepsy. MethodsCollecting the brain tissues of 24 patients with refractory epilepsy for surgical treatment from March 2010 to July 2011 as experimental group in hospitalized Epilepsy Center at the First Hospital of Jilin University, Changchun City. Collecting temporal lobe or frontal lobe brain tissue from 6 autopsy of patients who had emergency surgery for neurosurgery brain tranma during the same period. Using immunohistochemistry to observe the expression of p-mTOR, p-S6K1, p-4EBP1 in the two groups of brain tissues, and analyzed statistically. Results① p-mTOR, p-S6K1 and p-4EBP1 were expressed in both neurons and glial cells of experimental and control groups. P-mTOR, p-S6K1, p-4EBP1 positive cells of experimental group was significantly higher than the control group(P<0.01). The expression level of p-mTOR, p-S6K1, p-4EBP1 in the brain tissues of patients with different seizure frequency and with different duration:the expression level of p-mTOR, p-S6K1, p-4EBP1 in the brain tissues of patients in the group of epilepsy 10 years and more than 10 years were significantly higher than the group of epilepsy fewer than 10 years and the difference was statistically significant (P<0.05). ② The structural changes of brain tissues were observed under the optical microscope and electron microscope. Under the optical microscope:the distribution of nerve cells were uneven, the nucleus was vacuolated, the cytoplasm was less and gliosis. Under the transmission electron microscope:the number of neurons was reduced, nuclear condensation, the heterochromatin was increased, the nucleolus were dissymmetry and the nuclear membrane was breakage, also see neurons became psychotic, cell body became smaller, astrocyte cell membrane became edema, chromatin was dissymmetry, some mitochondrial were swelling and transparent, and others were vacuolated, the mitochondrial crista was in disorder. ③ p-mTOR, p-S6K1 and p-4EBP1 are expressed in the cerebral vascular of the brain in both experimental and control groups.In the experimental group, the expression is high concentration.In the control group, the expression is scattered in a small amount. Conclusionsp-mTOR, p-S6K1 and p-4EBP1 are widely expressed in neurons and glial cells with refractory epilepsy, which was significantly increased compared with control group. The expression of p-mTOR, p-S6K1and p-4EBP1 is related to frequency of epileptic seizures and course.