Ligustrazine(2,3,5,6-tetramethylpyrazine) is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease.The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present.This study summarizes its protective effect,the optimum time window of administration,and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury.We examine the effects of ligustrazine on suppressing excitatory amino acid release,promoting migration,differentiation and proliferation of endogenous neural stem cells.We also looked at its effects on angiogenesis and how it inhibits thrombosis,the inflammatory response,and apoptosis after cerebral ischemia.We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury.The time window of ligustrazine administration is limited.The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine,CXC137 and CXC195 after cerebral ischemia were better than ligustrazine. Ligustrazine (2,3,5,6-tetramethylpyrazine) is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use for ischemic cerebrovascular diseases remains unclear at present. study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia / reperfusion injury. We examined the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia / reperfusion injury. The time window of ligustrazine administration is limited.The protective effect and time window of a serie s of derivative monomers of ligustrazine such as 2 - [(1,1-dimethylethyl) oxidoimino] methyl] -3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine.