Intrauterine adhesion (IUA) is a common disease among women after uterus operation. BMSCs are commonly used as a therapeutic agent for IUA treatment, but the underlying mechanism is not fully delineated. Here we showed that BMSCs co-cultured with EPCs promotes proliferative ability and decreases apoptosis ratio of BMSCs and EPCs. In addition, BMSCs promote the differentiation of EPCs into vascular endothelial cells, and BMSCs derived epithelial cells are also induced by EPCs. We also found that the levels of Collagen Type I, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony stimulating factor (GM-CSF) and bone morphogenetic protein (BMP-2) are significantly increased in the co-culturing system comparing to those of the BMSCs or EPCs alone group. Of note, PI3K/Akt/Cox2 axis is activated in the co-culturing system and LY294002 abrogates the co-culturing system’s effects on cell proliferation, apoptosis and cytokines secretion, which are reversed by synergistically overexpressing Cox2. In conclusion, our in vitro experiments proved that the interaction of BMSCs and EPCs might promote angiogenesis and alleviate IUA pathogenesis by regulating PI3K/Akt/Cox2 axis mediated modulation of cell apoptosis, proliferation, differentiation and angiogenesis-associated cytokines secretion. © 2018, E-Century Publishing Corporation. All rights reserved.