Abstract Ischemic stroke remains to be a leading cause of death and disability worldwide at present. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathogenesis leading to a poor prognosis for ischemic stroke patients.Recent studies have found that miR155 may be involved in the occurrence of CIRI after stroke, but it’s role and specific mechanism are not completely clear.Therefore, this study investigated the effects of miR155 expression levels on mortality, cerebral infarction volume and neuronal apoptosis in MCAO/R rats by changing the expression level of miR155 in the ischemic penumbra (IP) region of rats. QRT-PCR and Western Blotting were used to detect the expression changes of Rheb, mTOR, 4EBP1 and S6K1 under different miR155 expression levels. The results showed that inhibition of miR155 could reduce the mortality, the volume of cerebral infarction and the number of neuronal apoptosis in MCAO/R rats.The mRNA and protein expressions of Rheb, mTOR, 4EBP1 and S6K1 were increased after inhibition of miR155, and vice versa. It suggested that inhibition the expression of miR155 could alleviate CIRI in the IP by activating Rheb/mTOR signaling at the transcriptional level. At the same time, we found that the phosphorylation level of mTOR signaling pathway were also increased after inhibition of miR155, indicating that autophagy level regulated by mTOR signaling pathway may be involved in the CIRI.