Objective To establish a model of indirectly induced respiratory tract infection in animals by influenza A (H1N1) and H3N2 subtypes viruses, to screen influenza virus transmission hosts, and to provide theoretical support for the clinical control of influenza viruses. Methods 50 BALB/c mice and 50 Hartley guinea pigs were randomly divided into 5 groups, which were normal control group, virus infection group 1, virus infection group 2, close transmission group 1, and close transmission group 2, with 10 animals in each group of each species. Mice in virus-infected group 1 and virus-infected group 2 were fed with influenza A (H1N1) and influenza A (H3N2) viruses via nasal drip, while guinea pigs in virus-infected group 1 and virus-infected group 2 were fed with influenza A (H1N1) and influenza A (H3N2) viruses via nasal drip; the animals in virus-infected group 1 were housed together with those in the close-transmission group 1:1 the following day, and the animals in virus-infected group 2 were housed together with those in the close-transmission group 1:1 the following day. Animals in virus infection group 1 were housed 1:1 with animals in close transmission group 1 the next day after infection, and animals in virus infection group 2 were housed 1:1 with animals in close transmission group 2 the next day after infection. On the 7th day, the lung function, viral titre and viral load of the nasal tissue, trachea and lung tissue of each group were measured, and the pathological changes of the trachea and lung tissue of the animals in the close transmission group were detected. Results Compared with the normal control group-mice, the viral titers and viral loads of nasal, tracheal and lung tissues of the virus-infected group 1 and 2-mice and the closely transmitted group 1 and 2-mice were significantly increased (P < 0.01), and the pathological scores of the trachea and lung tissues were significantly elevated (P < 0.01), and the FVC and FEV20 of the virus-infected group 1 and 2-mice were significantly decreased (P < 0.01); compared with the normal control group-guinea pigs, the FVC and FEV20 of the virus-infected group 1 and 2-mice were significantly decreased (P < 0.01). Compared with the normal control group-guinea pigs, the nasal tissue, trachea and lung tissues of virus-infected group 1 and 2-guinea pigs, and the nasal tissue, trachea and lung tissues of animals in the close transmission group 1 and 2-guinea pigs showed significant increases in viral titre and viral load (P < 0.01), significantly higher trachea and lung histopathological scores (P < 0.01), and significantly lower FVC and FEV200 (P < 0.01). Conclusion In this study, influenza A H1N1 and H3N2 subtypes influenza viruses were used to indirectly induce respiratory tract infections in mice and guinea pigs, respectively, and the models were evaluated in terms of animal lung function, respiratory viral titre, viral load and pathology. The animal model of indirect transmission of influenza viruses in the respiratory tract has certain limitations, in which influenza viruses are transmitted less efficiently among mice and more efficiently among guinea pigs, and the model is stable. This further confirms that guinea pigs have the characteristics of efficient replication and transmission of the virus..