Abstract: AIM:To evaluate the contribution of apelin, a novel peptide with significant cardioactive properties and the therapeutic efficacy of mesenchymal stem cells in hind limb ischemia mice. METHODS: Adipose-derived mesenchymal stem cells (AD-MSCs) expressing firefly luciferase (Fluc) were isolated from β-actin-luc mice and characterized by flow cytometry and bioluminescence imaging (BLI). Male FVB mice underwent femoral artery ligation and received AD-MSCs (1×106) or AD-MSCs with apelin intraquadriceps femoris muscle injection. Cell survival was imaged by BLI and expressions of Akt and pAkt after cellular therapy were analyzed by Western blot. RESULTS: In vivo BLI revealed acute donor cell death of AD-MSCs within 1 week after transplantation. In contrast, signals of injected cells were still present after 1 week in AD-MSCs in apelin group (P<0.05). In vitro apelin treatment of AD-MSCs exposed to hypoxia increased cell proliferation and considerable increases in phosphorylation of Akt were found in AD-MSCs pretreated with apelin. CONCLUSION: Apelin has beneficial effects on the therapeutic efficacy and survival maintenance of AD-MSCs in hind limb ischemia and may constitute an important target therapy in ischemic disease.