To investigate the effect of astragalosides (AST) and Panax notoginseng saponins (PNS) compatibility on the expression of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metal11oproteinase-1 (TIMP-1) after cerebral ischemia/reperfusion (I/R) injury in mice, to probe into its anti-ischemic brain injury protection mechanism. C57BL/6N mice were randomly divided into sham-operation group, model group, AST and PNS compatibility of high, medium and low-dose group, AST group, PNS group and edaravone group. Cerebral ischemia-reperfusion injury were prepared by bilateral common carotid artery ligation for 20 min followed by 24 hours reperfusion after administration for 4 days. Pathomorphism was detected with HE staining and the expression of MMP-9 and TIMP-1 protein in brain was detected by western-blot. The neuronal survival rate in the drug groups was significantly higher than the control group (P < 0.01), and the effect of the-middle dose compatibility group was more obvious. Factorial analysis manifested that AST110 mg x kg(-1) and PNS115 mg x kg(-1) compatibility had a synergistic interaction (P < 0.01). The expression of MMP-9 protein in the drug groups was lower than the model group significantly (P < 0.01 or P < 0.05), but the expression of TIMP-1 protein was higher than the model group significantly (P < 0.01 or P < 0.05), and the effect of the-middle dose compatibility group was more obvious, the two drugs had the stacking interaction (P < 0.05). AST110 mg x kg(-1) and PNS115 mg x kg(-1) compatibility has a synergistic effect against ischemia-reperfusion injury in mice by accommodating MMP-9/TIMP-1 probably.