Although bone tissue engineering techniques have become more and more sophisticated than in the past, natural bone healing mechanisms have not been sufficiently considered for further improvement of these techniques so far. We used an established animal model with transcriptome analysis to generate an unbiased picture of early bone healing to support tissue engineering concepts.In 30 Wistar rats, a 3-mm bone defect was created in the mandibular angle. Tissue was sampled at 5, 10, and 15 days, and the former defect area was excised to undergo transcriptome analysis after RNA extraction. Five differentially expressed genes were further evaluated with reverse transcription-polymerase chain reaction (rt-PCR).Transcriptome analysis revealed 2467 significantly over- and under-expressed transcripts after 5 days and 2265 after 15 days of bone healing, respectively. Validation via rt-PCR confirmed overexpression of osteoactivin, angiopoietin-like factor-4, and metallomatrix proteinase-9 and underexpression of mastcellprotease-10 and proteoglycane-2 in comparison to values in the control group.This systematic genome-wide transcriptome analysis helps to decipher the physiological mechanisms behind physiological bone healing. The exemplary depiction of 5 genes demonstrates the great complexity of metabolic processes during early bone healing. Here, BMP-2 signaling pathways and local hypoxia play decisive roles in bone formation.