Background/Aim: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery. Materials and Methods: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery. Results: Increased mRNA expression of transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group. Conclusion: Thyroid surgery leads to an actual increase of TGF-β1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.