Orthodontic tooth movement is considered as a biological response to the orthodontic stretch via the osteoblast and osteoclast processes. Orthodontic stretch leads to strain in the periodontal ligament, circulatory disturbances, and vascular changes of the periodontal tissue, which cause a hypoxic environment in local tissue. However, bone remodeling is not only induced by mechanical stress but also effected by hypoxic environment which regulated by numerous factors. Thus, we established a rat model of orthodontic tooth movement to investigate the expression and function of HIF-1α and VEGF in rat periodontal ligament under orthodontic stretch. The results showed that osteogenesis and vascular changes occurred in the tension site of alveolar bone during orthodontic tooth movement. Additionally, there were significant changes in the expression of HIF-1a and VEGF proteins under orthodontic force. Compared with control group, experimental group expressed significantly more HIF-1α and VEGF protein on the surface of the alveolar bone tension side during the rat tooth movement (p < 0.05). These data showed that the hypoxic environment could be induced by mechanical force. HIF-1a and VEGF may play an important role in maintaining the physiologic equilibrium of periodontal tissue reconstruction during orthodontic tooth movement.