Mechanical stimulation plays key roles in regulating the development and function of cells. With the rapid progress of space life science and space biotechnology, the biological behaviors of cells and the involved molecular mechanisms in space have gradually become a hot topic and frontier of the space biology. Bone marrow mesenchymal stem cells (MSCs) plays an important part in clinical cytotherapy and wound healing, due to its self renewal and multi-lineage differentiation potentials. In recent years, researchers have made significant achievements in biological behaviors of cells responding to microgravity environment by means of space simulation technology. In this review, some commonly used microgravity simulation devices were introduced, and changes in MSCs proliferation and differentiation under microgravity and its related molecular mechanisms were briefly summarized, so as to provide theoretical references for prevention and treatment of microgravity related diseases.