The aim of this study was to investigate the effect of Cystamine (CYS) on the hippocampal CA1 region in rats with whole cerebral ischemia. A total of 104 adult male Sprague-Dawley rats were prepared using the modified Pulsinelli method for a global Cerebral Ischemia (GI) model, and then randomly divided into a sham group (S, n=8), a GI group (GI, n=48), and a GI+CYS group (GI+CYS, n=48). The latter two groups were further divided into several subgroups according to the reperfusion time (6 h/12 h/1 d/3 d/5 d/7 d). Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to observe apoptosis in the CA1 region, and immunohistochemistry was used to detect the protein expressions of Brain-Derived Neurotrophic Factor (BDNF), Tyrosine kinase B (TrkB), and caspase-3. Compared with those in group S, the TUNEL-positive cells in the hippocampal CA1 region of group GI increased over time, but those in group GI+CYS were significantly decreased compared with those in group GI. Compared with group S, BDNF and TrkB proteins in group GI were upregulated, and reached a peak on d 1 (D1). Group GI+CYS exhibited a greater upregulation in these proteins than those group GI, and reached a peak on D1. The difference between these two groups was statistically significant. Compared with group S, caspase-3 protein in Group GI was upregulated and peaked on D3, but was lower in Group GI+CYS than in Group GI. The peak difference from that on D1 was statistically significant. CYS can inhibit apoptosis and upregulate BDNF and TrkB, thus exhibiting protective effects toward neurons subjected to ischemia-reperfusion in the hippocampal CA1 region.