This study aimed to identify potential miRNAs highly associated with the response to brain ischemic stroke. The miRNAs microarray expression profiles data were downloaded from Gene Expression Omnibus database under accession number GSE51586, including three ischemia and three ipsilateral normal samples from mouse brain tissues. Limma package was used to identify differentially expressed miRNAs between ischemia and ipsilateral normal samples. The common target genes of miRNA predicted from TargetScan, PicTar, miRanda and DIANA-microT databases were used as the candidate subset in which functional modules were identified by performing gene ontology enrichment analysis using ClusterProfile. Finally, the miRNA functional synergistic network was constructed by assembling all miRNA synergistic pairs. Fifty-one differentially expressed miRNAs were identified between ischemia and ipsilateral normal samples, including 32 up- and 19 down-regulated miRNAs. Among them, 24 miRNAs can commonly regulate at least one target gene and thus were used to construct a network, which included 274 pairs of co-regulating miRNAs. Further, 242 pairs of miRNAs interaction involving 23 miRNAs were shown to be synergetic in function. Sixteen miRNAs forming 20 miRNAs interaction pairs participated in inflammatory response, such as mir-185 and mir-674-3p. The 16 miRNAs related to inflammatory response during ischemic stroke may provide underlying targets for prevention and treatment of stroke.