Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. This article presents the hypotheses and current research that have furthered knowledge of the molecular biology that govern distraction osteogenesis. The gene regulation of growth factors and extracellular matrix proteins during distraction osteogenesis are discussed in this article. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.