During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1 alpha (HIF1 alpha) is stabilised in the periodontal ligament. While HIF1 alpha in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1 alpha. The present study was conducted to investigate the role of myeloid HIF1 alpha during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and HIF1 alpha(Delta myel) mice lacking HIF1 alpha expression in myeloid cells. Subsequently, mu CT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in HIF1 alpha(Delta myel) mice. This may be due to the lower bone density of the HIF1 alpha(Delta myel) mice. Deletion of myeloid HIF1 alpha was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1 alpha from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.