Objective : The purpose of this study is to investigate serial changes of hypoxia-inducible factor 1α (HIF-1α), as a key regulator of hypoxic ischemia, and apoptosis of hippocampus induced by bilateral carotid arteries occlusion (BCAO) in rats. Methods : Adult male Wistar rats were subjected to the permanent BCAO. The time points studied were 1, 2, 4, 8, and 12 weeks after occlusions, with n=6 animals subjected to BCAO, and n=2 to sham operation at each time point, and brains were fixed by intracardiac perfusion fixation with 4% neutral-buffered praraformaldehyde for brain section preparation. Immunohistochemistry (IHC), western blot and terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate HIF-1α expression and apoptosis. Results : In IHC and western blot, HIF-1α levels were found to reach the peak at the 2nd week in the hippocampus, while apoptotic neurons, in TU-NEL assay, were maximal at the 4th week in the hippocampus, especially in the cornu ammonis 1 (CA1) region. HIF-1α levels and apoptosis were found to fluctuate during the time course. Conclusion : This study showed that BCAO induces acute ischemic responses for about 4 weeks then chronic ischemia in the hippocampus. These in vivo data are the first to show the temporal sequence of apoptosis and HIF-1α expression.