To explore the key genes related to ischemia reperfusion injury (CIRI) by investigating the gene expression profile of the CIRI model in mice via bioinformatics analysis. Methods: The expression data of GSE23160 time series dataset associated with mouse cerebral injury was downloaded from Gene Expression Omnibus (GEO). The expression of gene expression profile of cortical brain tissue samples and striatum brain tissue samples at different time points after ischemia-reperfusion was analyzed. The underlying function of differentially expressed genes were predicted by GO and KEGG enrichment analysis. Then the cluster analysis was applied to identify the obvious trend of the differential genes for immune cell infiltration analysis and key genetic analysis. Consequently, the significant differentially expressed genes were verified in ischemia-reperfusion rats. Results: Immune cell infiltration analysis revealed that mast cells and macrophages were infiltrated during CIRI. CIRI gene differences major in the genes involved in callus, inflammatory response, and signal transduction pathway. Moreover, Timp1 and Gpr84 gene expression were significantly up-regulated in both tissues at different reperfusion time. Finally, the up-regulation of Timp1 and Gpr84 genes was further verified in ischemia-reperfusion rats. Conclusion: Our results suggest that Timp1 and Gpr84 genes may be the key genes in CIRI.