The present study was designed to investigate the role of microRNA‑451 (miRNA‑451) on cerebral ischemia‑reperfusion and to explore its possible mechanism. The expression of miRNA‑451 was downregulated in rats with cerebral ischemia‑reperfusion. In an in vitro model of cerebral ischemia‑reperfusion, the downregulation of miRNA‑451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)‑1b, IL‑6 and IL‑18. However, the upregulation of miRNA‑451 expression decreased inflammation in the same in vitro model of cerebral ischemia‑reperfusion. In addition, it was found that the downregulation of miRNA‑451 induced the expression of Toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor‑κB (NF‑κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF‑κB/p65 in the in vitro model of cerebral ischemia‑reperfusion, inhibiting the effects of miRNA‑451 upregulation on inflammation. A TLR4 inhibitor, TAK‑242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia‑reperfusion. TAK‑242 suppressed the effects of miRNA‑451 downregulation on inflammation. The present study suggested that miRNA‑451 regulated cerebral ischemia‑reperfusion‑induced inflammation, which is mediated through the TLR4/MyD88/NF‑κB signaling pathway.