Objective To observe the apoptosis of hippocampal dentate gyrus in rats with pentrolone model of epilepsy, and detect the significance of apoptosis-inducing factor (AIF) and Caspase-3 joint expression. Methods Twelve Wistar rats were randomly divided into model group and control group with 6 in each. Intraperitoneal injection of pentrolone was carried out for rats in the model group, while physiological saline was injected in rats of the control group. After the model was successfully established, we observed the Nissl staining results of hippocampus dentate gyrus tissue in the rats as well as the expression of AIF and Caspase-3 protein in both groups. Results The single visual nerve cell counts of the control group and the model group under 400-times magnification were respectively 99.76±11.89 and 78.69±10.94; Caspase-3 gray values of the two groups were respectively 154.81±16.06 and 131.65±16.81; and AIF protein gray values were respectively 173.09±9.57 and 158.34±6.33. All the above differences were statistically significant (P<0.05). Conclusion The two apoptotic pathways through Caspase-3 dependent on Caspase and AIF independent of Caspase are both involved in the neuronal apoptosis induced by epilepsy.