To investigate the changes in expression of p-Akt, Caspase-9, and Bcl-2 protein in the rat model of limb ischemic postconditioning (LIP) and examine the effect of the phosphatidylinositol 3-kinase/ Protein Kinase B (PI3K/PKB) signal transduction pathway in LIP against cerebral ischemia reperfusion injury in rats. Methods: A total of 42 Wistar rats were randomly assigned to the sham surgery group, ischemia/ reperfusion (IR) group, and LIP group with 14 rats in each group. The filament occlusion method was employed to generate the focal cerebral ischemia reperfusion model in the latter two groups. Two hours after the middle cerebral artery occlusion model was established and before reperfusion, LIP was carried out in LIP group rats by three cycles of 5 minutes occlusion/5 minutes release of the left femoral artery. Brain sections were stained with TTC for surveying the volume of infraction. The expression of p-Akt, Caspase-9, and Bcl-2 proteins was determined by immunohistochemical staining. Results: Compared with the IR group, the LIP group showed significantly decreased infarct volume (P＜0.05). The expression of p-Akt protein and Bcl-2 protein significantly increased in the LIP group compared with that in the IR group (P＜0.05). The expression of caspase-9 protein significantly decreased in the LIP group compared with that in the IR group (P＜0.05). Conclusion: Limb ischemic postconditioning may upregulate the expression of p-Akt and Bcl-2 proteins, downregulate the expression of caspase-9 protein, and reduce the cerebral infarct volume. The PI3K/PKB signal transduction pathway may play important roles in limb ischemic postconditioning against cerebral ischemia reperfusion injury.