Objective To explore the potential roles and mechanism of Wnt5a and its receptors in the pathogenesis of bronchiectasis. Methods From October 2017 to April 2018, outpatients with bronchiectasis who needed bronchoscopy were recruited in the Department of Respiratory and Critical Care Medicine of West China Hospital of Sichuan University. The control group was patients with pulmonary nodules less than 10 mm in diameter by health inspection. Patients who used antibiotics and/or glucocorticoids within the past 4 weeks or had other airway diseases were excluded. Serum and bronchial mucosa were collected for detection of Wnt5a by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR), respectively. The receptor of Wnt5a, Ror2, and the downstream pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, were measured in the bronchial mucosa by real-time PCR. Results From October 2017 to April 2018, 32 outpatients with bronchiectasis were found but only 17 patients finished this study, and simultaneously 18 patients with pulmonary nodules were chosen as control. The level of serum Wnt5a in patients with bronchiectasis were significantly higher than that in the control group (P<0.05). Correlation analyses showed that serum Wnt5a level was positively correlated with the level of serum C reactive protein (r=0.806, P<0.05), but had no relation with the level of white blood cell count, blood neutrophil percentage, pulmonary function or bronchiectasis severe index. The mRNA levels of Wnt5a and its receptor Ror2 in bronchial mucosa of patients with bronchiectasis were significantly higher than those in the control group (P<0.001). The mRNA levels of IL-1β and IL-6 in bronchial mucosa of patients with bronchiectasis were higher than those in the control group (P<0.05). Conclusion Wnt5a may play crucial roles in the development of bronchiectasis through Wnt5a/Ror2 signaling pathways to regulate the release of pro-inflammatory cytokines including IL-1β and IL-6.