Objective To better understand the dynamic pathological changes in the lungs of mouse and ferret models infected with novel avian-origin H7N9 subtype influenza virus. Methods A/Anhui/1/2013 (H7N9) virus was inoculated by intranasal instillation to mice and ferrets. Autopsies of 2-3 mice each time were performed on days 1, 2, 3, 5, 7, 14 and 28 post inoculation (d.p.i.) and 1 ferret on 3, 7, 14 and 28 d.p.i. Clinical signs and gross examination were conducted and histopathological analysis was performed. Results Animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), diarrhea(ferrets)and death (mice). Focal infection observed by gross examination and bronchitis and pneumonia determined by histology were seen in the lung in the mouse and ferret models. Inflammatory reaction was started from 2 d.p.i., most severe on 7-9 d.p.i. and absorbed from 14 to 28 d.p.i.. Lymphocytes and macrophages, especially CD8⁺ lymphocytes were increased in the lungs of infected mouse and ferret models. Conclusions Bronchitis and pneumonia can be induced in mice and ferrets inoculated with H7N9 virus. Inflammatory reactions are most severe on 7-9 d.p.i. and absorbed from 14 d.p.i., and infiltration of CD8⁺ lymphocytes is evident. Observation of pathological changes of the lungs in mouse and ferrets models enables detailed studies of the pathogenesis, diagnosis, treatment and prevention of this illness, and lays foundation for related drug or vaccine evaluation.