Bone homeostasis was signal transduction of osteoblasts ,osteoclasts and osteocytes, which proliferation and differentiation of stem cells participated in. Microgravity reduced the mechanical load which changed metabolism of bone cells in bone homeostasis. Review introduced the relations between microgravity and bone homeostasis. It explained mechanism of bone homeostasis. Microgravity delayed osteoblast histogenesis, enhanced absorption of osteoclasts, resulted in osteocyte osteolysis, in which macrophages mediated immune inflammation factor to regulate osteogenesis and bone resorption.The regulation mechanism of the skeletal system was complex, and multi-cell types interacted with each other. The cross-action of multi-signal pathways interacted with each other. In the further, it needed to explore the therapeutic targets of osteoporosis caused by dysregulation of bone homeostasis.