Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) interact with each other. EPCs are able to promote the self-renewal of MSCs as niche cells in murine bone marrow, and MSCs are able to promote EPC proliferation in vitro in a co-culture system. It has previously been reported that MSCs can secrete insulin-like growth factor-1 (IGF-1), which serves critical functions in EPC proliferation. However, the mechanism underlying the IGF-1-mediated proliferation of EPCs remains unclear. The aim of the present study was to reveal the molecular mechanisms regulating this process. The effects of IGF-1, which is secreted by MSCs, on EPC proliferation via the PI3K/Akt signaling pathway were examined by MTT assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. The present study treated EPCs with various concentrations of IGF-1. The results demonstrated that IGF-1 significantly induced the proliferation of cultured EPCs. However, this effect was offset by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results indicated that the pro-proliferative effects of IGF-1 are mediated in response to the PI3K/protein kinase B signaling pathway.