To observe the expression of let-7 and MKP1 in ischemia and reperfusion in mice brain tissue, and explore the relationship between let-7 and MKP1 on the basis of animals and cells. The cerebral ischemia and reperfusion model was constructed, let-7a, MKP1 expression levels in brain tissue were detected by RT-PCR and Western blot at different time points. By tail vein injection of let-7a inhibitor, the expression of let-7a was inhibited, then detected MKP1 expression by Western blot using neurological scores evaluated neurological function, and nerve cell apoptosis was observed by TUNEL staining. At the same time RT-PCR was used to detect the expression of inflammatory cytokines IL-6 and TNF-alpha in. In cultured PC12 cells, MKP1 gene and protein expression were measured and cell apoptosis was observed using TUNEL staining after over-expression or inhibition of let-7a, RT-PCR detected the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2. The results showed that let-7a highly expressed in the reperfusion brain tissue, Simultaneously, after tail vein injection, MKP1 expression significantly increased, mice neurologic impairment score decreased, brain tissue inflammatory cytokines IL-6 and TNF-alpha also significantly lower, and the degree of neuronal apoptosis significantly reduced; cell experiments suggested that transfection of let-7a analogs could down regulate the expression of MKP1 gene and protein in PC12 cells, promote the expression of pro-apoptotic protein Bax and inhibit anti-apoptotic protein Bcl-2, thereby promoting apoptosis. Transfection of let-7a inhibitor could promote the MKP1 expression of genes and proteins, inhibit the expression of pro-apoptotic protein Bax and promote anti-apoptotic protein Bcl-2, thereby reducing apoptosis of PC12 cells. Let-7a targeted regulated MKP1, and involved in MAPK signaling pathway, which leads to Inflammation and Apoptosis of Nerve cells reperfusion. This study provided a new direction for the study of cerebral ischemia and reperfusion basic clinical treatment.