Objective To establish the Influenza H5N1 influenza virus infection ferrets animal model． Methods Groups of three 4-to 6-month -old ferrets were inoculated intranasally with 103 and 104 TCID50 of H5N1 A /Vietnam /1203 /2004 in a volume of 500uL． Ferrets were monitored daily for clinical signs of influenza infection，and body temperatures were recorded once daily． Every day take nasal turbinates for RT-PCR． On day 5 postinoculation，ferrets were euthanized and trachea，lung，heart，liver，slpeen，kidney，small intestine，and brain tissue were harvested，and examined by light microscopy． Results For each titer virus tested，in infected ferrets，we observed fever，weight loss，nasal rattling，sneezing and died． Virus was detected in the nasal turbinates and heart，liver，slpeen，kidney，small intestine，and brain from all of the iinfected ferrets． Of the ferrets inoculated with H5N1 virus，there show focal severe pneumonia in lung．Conclusions In clinical signs，virus detection，and histological changes were observed ferrets were infected H5N1 influenza virus，which 104 TCID50 titer was a more appropriate to establish flu animal models．