Objective To investigate the importance of histone acetyltransferase (HAT) activity on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic mice.Methods A mouse model of asthma was constructed. Peripheral blood was routinely analyzed, alveolar lavage fluid was routinely stained and counted, HE staining was performed in the lung tissue, and MUC5AC protein expression in lung tissue was detected by immunohistochemistry. ELISA was used to determine HAT, histone deacetylase (HDAC) activity, and MUC5AC level. Then statistical analyses were performed.Results Peripheral blood eosinophil count (EOS) in asthma group was higher than that of trichostatin A (TSA) treatment group and control group (P < 0.05). Total cells and EOS of alveolar lavage fluid in asthma group were higher than those of TSA treatment group and control group (P < 0.05). TSA treatment and asthma group can simultaneously reduce the activity of HAT and HDAC in mice (P < 0.05), but mainly HAT. MUC5AC levels in the TSA treatment group were lower than those in the asthma group (P < 0.05). HE staining of lung tissue showed that inflammatory cells in the tract of asthmatic group increased, but significantly improved after TSA treatment. Immunohistochemical results showed that the TSA treatment group can significantly reduce the MUC5AC protein content compared with the asthma group (P < 0.05).Conclusion Histone acetylation plays an important role in the regulation of airway mucus secretion in asthmatic mice.