Mesenchymal stem cells (MSCs) derived from bone marrow have shown great promise in tissue repair. While these cells induce little immune response, they show marked self-renewal properties and can differentiate into many cell types. Recent evidence shows that mechanical factors such as fluid shear stress, mechanical strain and the rigidity of extracellular matrix can regulate the proliferation and differentiation of MSCs through various signaling pathways. Transplanted MSCs enhance angiogenesis and contribute to remodeling of the vasculature. In this review, we will focus on the responses of vascular cells and MSCs to shear stress, strain and matrix rigidity and will discuss the use of MSCs in myocardial repair and vascular tissue engineering.