Objective To establish a model of asthma mice with spleen-deficiency syndrome (asthma-SDS) and to investigate the effects of Cryptoporus volvatus ferment substance (CVFS) on the airway hyperresponsiveness and inflammation in model mice. Methods An asthma-SDS model of mice was established by ovalbumin (OVA)-sensitized plus over-eating and over-exerting. The changes of lung resistance (R_L), inflammatory cells in bronchoalveolar lavage fluid (BALF), lung tissue pathology, and spleen index were observed. Results Compared with the simple asthma model of mice, the airway hyperresponsiveness, eosinophils number in the BALF, lung tissue pathology, and spleen index in the asthma-SDS model of mice showed a significant difference (P