Remote ischemic conditioning (RIC), as an emerging protective method, might be used clinically to prevent ischemia-reperfusion injury (IRI) in ischemic stroke. In this study, we aim to investigate whether RIC performed either during brain ischemia or after reperfusion has a protective effect and further explore the mechanistic basis for the protective effects of RIC against IRI in an aged rat model. We investigated brain IRI in 16-18 months old SD rats. Animals underwent: (i) sham laparotomy, (ii) brain IRI, (iii) brain IRI  +  RIC during ischemia (IRI  +  RIperC), or (iv) brain IRI  +  RIC after reperfusion (IRI  +  RIpostC). RIC consists of three cycles of 10 min of hind limb ischemia followed by 10 min reperfusion. After 24 h of reperfusion, the infarct size, neurological deficit scores and brain oedema were assessed in all groups. The levels of IL-1β, IL-6, TNF-α were measured by ELISA. The mRNA and protein expressions of TLR4, MyD88, TRAF6 and NF-κB were detected by RT-PCR and western blot. Both RIperC and RIpostC treatment attenuated the IRI-induced neuronal injury, reflected by reductions in the infarct size, neurological deficit scores and brain oedema. RIperC and RIpostC also can decrease the concentration of IL-1β, IL-6, TNF-α in IRI. From the results of RT-PCR and western blot, we found that RIC decreased the mRNA and protein expression of TLR4, MyD88, TRAF6 and NF-κB compared to that in the IRI group. The present study suggested that RIC protected aged rats against IRI, and this protective effect might be mediated by inhibiting the TLR-4/MyD88/TRAF-6/NF-κB signaling pathway.