Objective To establish a model of indirectly induced respiratory tract infection with influenza A subtypes H1N1 and H3N2 in animals, to screen influenza virus hosts, and to provide theoretical support for the clinical control of influenza viruses. Methods Fifty BALB/c mice and 50 Hartley guinea pigs were randomly divided into five groups (10 animals/group for each species): normal control group, virus infects 1 group, virus infects 2 group, close transmission 1 group, and close transmission 2 group. Mice and guinea pigs in virus infects 1 and 2 groups were administered influenza A (H1N1) and influenza A (H3N2) viruses via nasal drip. For both virus infects 1 and 2 groups, animals were housed together with those in the close transmission group at a 1 ∶ 1 ratio on the following day. On day 7, the lung function, viral titer and viral load of the nasal tissue, trachea, and lung tissue of each group were measured, and pathological changes of the trachea and lung tissue of animals in the close transmission group were evaluated. Results In mice, the viral titers and viral loads of nasal, tracheal, and lung tissues of virus infects 1 and 2 and the closely transmitted groups 1 and 2 were significantly higher (P<0.01), pathological scores of the trachea and lung tissues were significantly higher (P<0.01), and the FVC and FEV₂₀ of virus infects 1 and 2 groups were significantly lower (P<0.01) than those in the normal control group. The nasal tissue, trachea and lung tissues of guinea pigs in virus infects 1 and 2 groups and close transmission groups 1 and 2 showed significantly higher viral titers and viral loads (P<0.01), significantly higher trachea and lung histopathological scores (P<0.01), and significantly lower FVC and FEV₂₀₀ (P<0.01) than those of the normal control group. Conclusions In this study, influenza A subtypes H1N1 and H3N2 were used to indirectly induce respiratory tract infections in mice and guinea pigs for analyses of animal lung function, respiratory viral titers, viral load, and pathology. The animal models of the indirect transmission of influenza viruses in the respiratory tract had certain limitations; for example, influenza viruses were transmitted less efficiently among mice than among guinea pigs. The guinea pig model was stable. These findings confirm that guinea pigs are suitable hosts for efficient virus replication and transmission.