Background and Objectives: Empty nose syndrome (ENS) is a debilitating condition that often results from traumatic or iatrogenic causes, such as nasal surgery. There are various conservative and surgical treatments for ENS, but their effectiveness remains uncertain. Therefore, the development of animal models that accurately mimic human ENS is essential for advancing effective treatment strategies. Materials and Methods: To investigate ENS development, turbinoplasty was performed in the nasal cavity of swine, entailing partial removal of the ventral turbinate using turbinectomy scissors followed by electrocauterization. After 56 days, samples were obtained for histological and morphological analyses. Results: A significant reduction in the volume of the ventral turbinate in the ENS model led to an expansion of the nasal cavity. Histological analysis revealed mucosal epithelial changes similar to those observed in ENS patients, including squamous cell metaplasia, goblet cell metaplasia, submucosal fibrosis, and glandular atrophy. Biomarkers related to these histopathological features were identified, and signals potentially contributing to squamous cell metaplasia were elucidated. Conclusions: The swine ENS model is anticipated to be instrumental in unraveling the pathogenesis of ENS and may also be useful for evaluating the effectiveness of various treatments for ENS.