Objective To establish a stable mouse model of pneumonia enteritis caused by H1N1 influenza virus,and provide tools and means for study of the pathological basis of gastrointestinal influenza and antiviral drugs. Methods Experimental mice were randomly divided intofour groups ( n= 6): 10 TCID₅₀ , 1 TCID₅₀ , 0. 1 TCID₅₀ and control. All mice except the control group were intranasally infected with different doses of H1N1 influenza virus. After infection with the virus, the anal temperature and body weight of mice were measured every day, and their fur and mental state were observed for 7 consecutive days. After death, the organ index of mice was measured and mRNA expression of the H1N1 Mgene of influenza virus in lung tissue and ROR-γt in small intestine were detected by RT-PCR. Results Compared with the control group, the body weight of model group mice in 10 TCID₅₀ and 1 TCID₅₀ groups decreased significantly, the lung index increased significantly (P<0. 01), the thymus index decreased significantly (P<0. 01 and P<0. 05, respectively), and mRNA expression of the H1N1 M gene of influenza virus and ROR-γt in small intestine increased significantly (P<0. 01 and P< 0. 05, respectively). The mortality of 10 TCID₅₀ and 1 TCID₅₀ groups were 67% and 17%, respectively, while the other groups were 0. Although there were similar trends in indexes of the 0. 1 TCID₅₀ group, there was no significant difference. An infection dose of 1 TCID₅₀ was verified. Compared with the control group, the result of histological sections displayed serious pathological injuries in the lung and small intestine of the model group. Moreover, relative expression of IL-2, IL-6, IFN-γ and IL-17A in the lung tissue, as well as GM-CSF and IL-2 in small intestine, was significantly increased; in contrast, IL-6 and IL-33 in intestine were significantly decreased. Conclusions 1 TCID₅₀ virus infection was the best concentration for establishing a mouse pneumonia enteritis model. The establishment method of this model is stable and reliable, providing a good pathological model for antiviral research.