Objective To observe the effect of Cystamine on the chronological expression of tissue-type transglutaminase after the hippocampal region of global cerebral ischemia-reperfusion injury in rats. Methods The experimental global cerebral ischemia-reperfusion injury model was established by the method of 4-vessel occlusion.The Sprague-Dawley rats were randomly divided into sham-operated group (n=8), global cerebral ischemia group (n=48) and global cerebral ischemia treatment group(n=48) . Global cerebral ischemia group and global cerebral ischemia treatment group were divided into six subsets such as 6,12hour,1,3,5,7day according to the time point with 8 rats. Cystamine was injected intraperitoneally[0.15mg/(g·day)]10 minutes after cerebral ischemia for global cerebral ischemia treatment group. Saline was injected intraperitoneally for global cerebral ischemia group and shamoperated group. Neurons apoptosis was detected by TUNEL technology and the expression of tTG was detected by Immunohistochemistry(SP)in the hippocampal CA1 region of different time points.The other 52 rats were randomly divided into sham-operated group(n=4) , global cerebral ischemia group(n=24) and global cerebral ischemia treatment group (n=24). Global cerebral ischemia group and global cerebral ischemia treatment group were divided into six subsets according tothe time point with 4 rats.The expression of tTG was detected by Western blotting. Results About 24h after ischemiareperfusion injury ,the positive cells of TUNEL staining were significantly increased. Compared to the sham-operated group, the positive cells of TUNEL at the subset 1, 3, 5, 7day after global cerebral ischemia group were significantly increased(P<0.05).The number of apoptotic cells in subset 1, 3, 5, 7day of global cerebral ischemia treatment group were significantly less than that of global cerebral ischemia group (P<0.05). In global cerebral ischemia treatment group, tTG immunopositive cells began to decrease in the CA1 region of hippocampus in subset 12hour time point,and significantly decreased in 3, 5, 7day subset of global cerebral ischemia group(P<0.05). In global cerebral ischemia treatment group, tTG protein level began to increase 1 days after ischemia-reperfusion, and significantly decreased in 3, 5, 7day subset of global cerebral ischemia group(P<0.05). Conclusion Cystamine can reduce the expression of tTG after the hippocampal CA1 region of global cerebral ischemiareperfusion injury in rats, which might be the mechanism of protecting ischemic injury of neurons.