Objective To observe the mechanism of endoplasmic reticul stress (ERS) on the expression of mucin 5AC (MUC5AC) in respiratory mucosal epithelial cells of asthmatic rats. Methods Fifty rats were randomly divided into control group, ovalbumin (OVA) group, small interfering RNA (siRNA) group, negative control (NC) group and 4 phenylbutyric acid (4-PBA) group with 10 rats in each group. In addition to the control group, the other groups were established asthma model by ova. After corresponding intervention, Penh value of each group was compared; The percentagesof neutrophils, eosinophils and lymphocytes in BALF were calculated; IL-4 and IFN-4 were detected in BALF-γ Level; The pathological changes of lung tissue were observed; Sec61, GRP78, chop and MUC5AC were detected. Results Compared with the control group, the total number of cells, neutrophils, eosinophils, percentage of lymphocytes, IL-4, Sec61, GRP78, chop and MUC5AC in Penh and BALF of ova group were increased, while IFN 4, Sec61, GRP78, chop and MUC5AC were increased γ0 Compared with OVA group, the total number of cells, neutrophils, eosinophils, percentage of lymphocytes, IL-4, Sec61, GRP78, chop and MUC5AC in Penh and BALF of siRNA group were lower than those of ova group γ0 He staining showed that goblet cells proliferated, bronchial wall thickened and inflammatory cells infiltrated in ova group. The pathology of siRNA group was better than that of ova group.Conclusion Sec61 may affect the expression of MUC5AC by regulating ERS, and participate in the occurrence and development of asthma.