Background and objective Exposure to inorganic dust and particulate matter (PM) disrupts the integrity and function of the airway epithelial barrier (AEB). Herein, the immune response and epithelial barrier integrity disruption effect of respirable ex vivo airway tissue models. Methods Particles at an average size of 1 µm, referred to as ex vivo. Computational fluid dynamics simulations were performed to assess shear stress profiles under different flow conditions. WST-1, LDH, SEM, ELISA, IF and qRT-PCR analyses were carried out to evaluate cell survivability, morphology, barrier integrity and inflammation. Results In AEB-on-a-chip platform, the exposure to PM2.5 dusts disrupted AEB integrity via decreasing cell adhesion-barrier markers such as ZO-1, Vinculin, ACE2 and CD31, impaired cell viability and increased the expression levels of proinflammatory markers; IFNs, IL-6, IL-1s, TNF-α, CD68, CD80, and Inos, mostly under dynamic conditions. Besides, decreased tissue viability, impaired tissue integrity via decreasing of Vinculin, ACE2, β-catenin and E-cadherin, and also proinflammatory response with elevated CD68, IL-1α , IL-6, IFN-Ɣ, Inos and CD80 markers, were observed after PM2.5 dust exposure in ex vivo tissue. Conclusion The disruption of the barrier integrity and subacute immune response upon silica PM2.5 exposures is nicely demonstrated by both AEB-on-a-chip platform emulating dynamic forces in the body and resident immune cells containing ex vivo bronchial biopsy slices. Airborne dust pollutants pose a significant future respiratory hazard for human airways under climate change conditions and Lung-on-a-Chip Models will serve as reliable substitutes in this context.