Objective:To observe the effect of gastrodine on p-AKT and caspase 3 in rats with epilepsy induced by pentylenetetrazole (PTZ). Methods69 Wistar rats were assigned into blank control group (18 rats), epilepsy model group (PTZ group, pentylenetetrazole, 55~75 mg/kg) (28 rats) and gastrodine group (Gas group, gastrodine, 200 mg/kg) (23 rats). Epileptic model was established with rats in all of groups by PTZ intraperitoneal injection except the blank control group. Gastrodine was given to the Gas group. Histomorphological changes of hippocampus were observed under electron microscope. The expression of serine-threonine protein kinase (p-AKT) and cysteine-aspartic acid specific protease 3 (caspase 3) in hippocampus was detected by immunohistochemistry and Western blotting.  Results:Compared with the control group, the hippocampal area of the PTZ group showed remarkable pathological changes of epilepsy, including significant neuronal degeneration and necrosis, mainly the large pyramidal cells and some dentate gyrus granulosa cells, nucleus condensation in damaged cells, fragmentation-like nuclear changes, cytosolic swelling, disappearance of the nissl bodies and increase in cell peripheral gap and cell volume. The pathological changes were improved after drug intervention. After seizure in rats, the expression of p-AKT and caspase-3 was higher in the epilepsy model group than in the blank control group (P<0.05). Compared with the epilepsy model group, the expression of caspase-3 decreased in the gastrodine group (P<0.05), with very significant difference at day 3 between the two groups (P<0.01).  Conclusion:Gastrodine plays an anti-apoptotic role and protects against epilepsy by reducing the expression of p-AKT and caspase 3.