The effects of stretch sensitive positive ion channel, the internal flow of Ca(2+) and myristoylated alanine-rich C kinase substrate (MARCKS) on the high externalization of MUC5AC in airway epithelial cells in mechanical stretching.Mini-type Multi-functional Bio-impact Machin was used to construct the model of mechanical stretching. The airway epithelial cells were divide into control group, stretch, stretch and gadolinium, stretch and low molecular weight heparin, stretch and nifedipine, stretch and the locked nucleic acids of MARCKS effective domain (ED), stretch and the control locked nucleic acids of MARCKS ED groups. The expression of MUC5AC and SNAP23 protein in cells were determined by immunohistochemistry method, contents of MUC5AC and SNAP23 protein were measured by Image Pro Plus 5.0. MUC5AC protein in supernatant was determined by ELISA methods. SNAP23 mRNA was determined by RT-PCR methods.Mechanical stretching could increase the expression of SNAP23 and MUC5AC in cells and MUC5AC in supernatant (P < 0.05). Gadolinium, nifedipine and LNA of MARCKS ED could reduce the increase the expression of SNAP23 and MUC5AC in cells and MUC5AC in supernatant (all P < 0.05).Mechanical stretching could increase the expression of MUC5AC in airway epithelial cells. This maybe is concerned with stretch sensitive positive ion channel, the internal flow of Ca(2+) and MARCKS.