Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops. Methods Seventy-two BALB/c mice were divided randomly into nine groups: a Control group, wind-heat(FR) groups (FR-3Day, FR-5Day), and Model groups (1LD-3Day, 2LD-3Day, 3LD-3Day, 1LD-5Day, 2LD-5Day, 2LD-5Day, 3LD-5Day) (n= mice per group). Mice in the Control group were housed in a normal environment, while mice in the FR and Model groups were kept in wind-heat conditions for 7 d. Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day, and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops. After virus challenge, each group was housed in a normal environment and samples were taken on days 3 and 5. The appearance of the mice was observed and recorded and the lung index, routine blood parameters, lung tissue pathology, serum interleukin (IL)6 levels, and virus titers were detected in each group based on their behavioral status, stools, and body temperature. Results After 7 d of wind-heat intervention, mice in the FR groups showed no significant abnormalities in terms of appearance, stools, body temperature, routine blood parameters, or lung tissue pathology compared with the Control group. The appearance, lung index, red blood cell count, hemoglobin, hematocrit, pathological result, and body temperature in the Model groups worsened progressively with increasing time and toxin dosage, while the neutrophil percentage, lymphocyte percentage, virus titer, and serum IL-6 levels peaked on day 3 after viral attack, for the same viral dose, and then decreased slightly on day 5. Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.