Objective To filter appropriate mouse model for avian influenza viruses with different pathogenicity.Methods Two varieties mice (C57BL/6 and BALB/c) were anesthetized with ketamine and inoculated intranasal with highly pathogenic avian influenza virus H7N9 and low pathogenic avian influenza virus H9N2 in 50 μl PBS,or mock inoculated with PBS to serve as controls.The mice were observed daily including clinical symptoms body,weight and mortality.The pulmonary histopathological changes and viral load were also monitored.Results Just one day after the viral inoculation,H7N9 and H9N2 infected mice strains all showed reduced activity,ruffled fur and obvious body weight loss.The body weight loss nadir in BALB/c mice (63.80％ for H7N9/BALB/c;66.35％ for H9N2/BALB/c) were lower comparing to the corresponding viruses infected C57BL/6 mice (68.96％ for H7N9/C57BL/6 and 87.57％ for H9N2/ C57BL/6 respectively).In addition,there were some obvious pulmonary oedema,haemorrhage and typical pulmonary interstitial inflammatory lesions in the lung tissues.The peak viral load in H7N9/C57BL/6 group (1.02 × 105 copies/ml) was 12 folds higher than that in H7N9/BALB/c group (8.7 × 103 copies/ml).But on the contrary,the peak viral load in H9N2/BALB/c group (2.86 × 104 copies/ml) was 5 times of that in H9N2/C57BL/6 group (5.94 × 103 copies/ml).Conclusions Pathogenic characteristics caused by different virulent avian influenza viral strains could be more clearly differential represented in C57BL/6 mice model,and thus it is more suitable for the comparative study between different pathogenic avian influenza viruses.It also reconfirmed that the different pathological changes and clinical outcomes of avian influenza viruses/mice infection models were associated not only to the different biological characteristics of inoculated virus strains,but also to hereditary characters of host mice strains.