Abstract: Objective To study the changes of orexin-A cells and their nerve fibers in a rat epilepsy model at different time points. Methods Seizure of rats was induced by intraperitoneal injection of kainic acid.Changes of orexin-A immunoreactive cells and their nerve fibers were detected by immunohistochemistry 8h,1,3,7 days and chronic relapsing time after epilepsy,respectively. Results The orexin-A immunoreactive cells were mainly distributed in the hypothalamus and perifornical nuclei and their immunoreactive nerve fibers were widely distributed.The number of orexin-A immunoreactive cells was lower while the number of their nerve fibers was significantly higher at 8h after epilepsy than at the other time points after epilepsy.The number of orexin-A immunoreactive cells was decreased at first,then recovered,and decreased again.The average optical density curve of their immunoreactive fibers ascended at first,then descended after recovery,and ascended again. Conclusion Changes of orexin-A immunoreactive cells and their immunoreactive fibers at different time points after epilepsy show that they may participate in the regulation of epilepsy.