Background: Asthma characterized by airway hyperresponsiveness, increased inflammatory cells, and fibrosis and angiogenesis. SRY-related HMG-box 18 (SOX18) is an important transcription factor involved in the development of cardiovascular and lymphatic vessels during embryonic development and wound-healing processes. SOX18 remains to be clarified in asthma. Objective: In this study we aimed to elucidate the role of SOX18 in the pathogenesis of bronchial asthma. Methods: Using an established mouse model of ovalbumin (OVA)-induced chronic allergic asthma, we investigated whether SOX18 is involved in pathogenesis of asthma. Airway hyperresponsiveness (AHR) was measured and bronchoalveolar lavage fluid was collected, lung tissue was processed for protein and RNA, and hematoxylin and eosin stain. Collagen was measured by trichrome stain and sircol assay. SOX18 level checked in lung human microvascular endothelial cells (HMVEC-L) and normal human bronchial epithelial (NHBE) cells treated with house dust mite (HDM). Moreover, we observed SOX18 levels in blood from asthmatic patients between stable and exacerbated state. Results: The chronic asthma mice showed that SOX18, PROX1, COUP-TFII, mucous gland hyperplasia and collagen deposition in lung tissue were significantly increased after OVA challenge. SOX18 protein in HMVEC-L and NHBE cells was increased following HDM treatment. PROX1 and COUP-TFII protein in HMVEC-L were decreased and increased in NHBE cells following HDM treatment. SOX18 in blood from exacerbated asthmatics was increased compared with those from stable asthmatics. Conclusion: These results suggesting that SOX18 may be associated with asthma exacerbation and can be a biomarker for asthma.