Mechanical stress plays an important role in bone growth and bone remodeling. It causes stretch stress and fluid flow shear stress, which can be sensed by mechano-sensory cells, e.g. osteocyte and osteoblast, and induces changes of gene expression in those cells. The fluid flow shear stress is thought to be the main stimulin in this process. However, up to now, it is still not clear for what signals are triggered in mechano-sensory cells and how the flow shear stress exactly affects the expression of specific proteins. Evidences have shown that the stress-sensitive cation channels, the integrin-cytoskeleton complexes and the gap junction/CX43 hemi-channels may be key players in transducing mechanical signals, presumably via mitogen-activated protein kinase pathway, PKA/PKC pathway, NFκB pathway, RhoA/ROCK pathway and Ca(superscript 2+) signaling pathway. At the far end of the response, there is evidence for regulation at the level of gene transcription. For example, the production of cell growth factors, transcription factors and osteogenic proteins is enhanced significantly in osteocytes and osteoblasts after FSS stimulation. The precise mechanism involved in mechano-transduction and signal transduction remains to be elucidated.