Abstract: Objective To establish a tree shrew model of H1N1 influenza virus infection and to explore the dynamics of the influenza virus and its distribution in respiratory tissues. Methods Twenty-four 3 to 3.5-years-old adult tree shrews (Tupaia Belangeri Chinensis), with equal numbers of males and females, were randomly divided into a blank group (group B) and a model group ( group M) of 12 tree shrews each. H1N1 influenza virus 600 μL/ bird (1 ×106.8 TCID50 / 0. 1 mL) were inoculated into M group tree shrews through the nasal cavity; the rectal temperature was measured every morning from rom 3 d before until 10 d after inoculation, and throat swabs, nasal swabs, and blood samples were collected to determine the viral load. Blood levels of neutralizing antibodies against influenza were determined on days 2, 4, and 7. Three tree shrews were randomly sacrificed on days 2, 3, 5,and 10, turbinate, trachea, pharynx, and lung tissues were collected for viral load detection, 3, 5, and 10 days of tissue were taken for histopathology. Results Tree shrews in group M showed clinical symptoms such as a disheveled coat, loss of appetite, slow movement, increased body temperature, and increased nasopharyngeal secretion, and their blood viral load appeared. There were some pathological changes to the turbinate, pharynx, trachea, and lung tissue of group M. Conclusions The clinical symptoms of tree shrews infected with influenza virus were very similar to those of humans. The established influenza virus tree shrew model provides a valuable tool for studying the pathogenesis of influenza and evaluating anti-influenza drugs.