Abstract: Objective To study the effect and possible protective mechanism of tetramethyl pyrazine(TMP) on cerebral ischemia/reperfusion in jury in gerbils.Methods Male gerbils were divided randomly into four groups:control group,ischemia/reperfusion group(I/R),ischemia preconditioning group(IP),and TMP preconditioning group.Changes of neuron morphous in hippocam pus region were observed by HE staining.The expression level of glial fibrillary acidic prote in (GFAP) was detected with mimunohisto chemistry.Neuron apoptosis was detected with term inal deoxynucleotidyl transferase mediatedd UTP nick end labeling (TUNEL) method.Learning-memory function was determined with 4-pellet taking test (4PTT) dry path maze.Results Compared with I/R group,the density of survival neurons(12.93±3.17,18.74±4.21) and the expression levels of GFAP(8.50±1.25,12.72±1.38) were enhanced in IP group and TMP preconditioning group,and the apoptotic neurons(16.50±5.25,9.72±3.38) were decreased.Reference memory index and working memory index were miproved(P < 0.05 for all).Conclusion TMP can improve learning memory function in gerbils with cerebral ischemia/reperfusion damage and enhance ischemic to lerance,which might be associated with up-regulation of GFAP expression and down regulation of neuron apoptosis.