Abstract: 【Abstract】 Objective To explore if ischemia preconditioning of lower limbs could protect the local ischemia reperfusion damage in rat brain and the role of neural pathways during the process. Methods Fifty male Sprague-Dawley rats were randomly assigned into five groups (n=10 for each group). Group Ⅰ was sham group. Group Ⅱ was the occlusion of middle cerebral artery (MCAO) for 90 min. Group Ⅲ was remote ischemic preconditioning (RIPC) 24 h before MCAO. Group Ⅳ was femoral nerve and sciatic nerve (FS) resected before RIPC and MCAO. Group Ⅴ was FS resected only before MCAO. All the rats in the later four groups were subjected to brain reperfusion after MCAO for 90 min. The brain samples were harvested 24 h after MCAO for the evaluation of neuroligical deficit score (NDS) and infarct volume, histomorphlogical study with HE staining, as well as the evaluation of neuron apoptosis with TUNEL staining and Caspase-3 staining. Results The infarct volume in group RIPC+MCAO （18.24%） was smaller than that in MCAO group (30.92%), and TUNEL and Caspase-3 staining also demonstrated significantly lesser apoptotic neurons (20.81, 5.78) in comparison with MCAO group (45.23, 12.94). However, the infarct volume (28.77%) and apoptotic neurons (53, 11.83) of FS+ RIPC +MCAO group did not show statistical difference when compared with those of MCAO group. The results of NDS and HE staining in RIPC+MCAO group were better than those in MCAO group, while they showed no statistical difference in the condition of nerve resected before RIPC+MCAO when compared with MCAO group. Conclusion The ischemia preconditioning of lower limbs may provide protection on ischemia-reperfusion injury in rats brain through neural pathways.