Objective To study the protective effect of a Chinese medicine,Shenmai injection, on brain tissue in a mouse model of cerebral ischemia and explore its possible mechanism. Methods Thirty healthy adult male CD-1 micewere randomly divided into control, model, and experimental groups with 10 mice in each group. The mouse model of acutecerebral infarction was established by permanent middle cerebral artery occlusion. The experimental group was treated withShenmai injection. The control and model groups were administered the same dose of physiological saline. The red blood cellfunctional indexes were compared among groups. The neuonal apoptosis rate of brain tissue was determined by TUNELassay. Calpain-1 and Bcl-2 expression in the mouse cortex was detected by Western blot and qPCR. Results Comparedwith the control group, RBC-C3bR was significantly decreased and RBC-ICR was significantly increased in the experimentalgroup ( P < 0. 05). Compared with the model group, RBC-C3bR was significantly increased, and RBC-ICR was decreasedsignificantly in the experimental group( P < 0. 05). The number of TUNEL-positive cells in the brain tissue sections ofmodel and experimental groups was significantly higher than that of the control group ( P < 0. 05). The number of TUNELpositivecells in brain tissue sections of the experimental group was significantly lower than that of the model group ( P <0. 05). Compared with the control group, the expression levels of calpain-1 protein and mRNA in model and experimentalgroups were significantly increased, and the expression levels of Bcl-2 protein and mRNA were decreased significantly ( P <0. 05). Compared with the experimental group, the expression levels of calpain-1 protein and mRNA were significantlydecreased, and that of Bcl-2 protein and mRNA were increased significantly ( P < 0. 05). Conclusions Shenmai injectionimproves erythrocyte functions and inhibites neuronal apoptosis in this mouse model of cerebral infarction. The possiblemechanism of the protective effect of Shenmai injection on brain infarction may be the downregulating of expression of calpain-1 protein and upregulating of expression of anti-apoptotic protein Bcl-2 in the brain tissues.