The health ministry said virology tests, carried out with the collaboration of the World Health Organisation (WHO) in Cairo, showed that the samples were positive for the virulent strain of the flu virus.
"Tests from a person suffering from flu-like symptoms on April 27 were positive for the disease," the ministry said in a statement read on state radio. "Three domestic hens were also affected by the virus."
The condition or identity of the infected person was not released by the health ministry, but it did say that the person had been in direct contact with infected fowl. It called on the population to avoid proximity to live birds and report suspicious deaths of fowl.
The ministry added that the government was taking "all necessary precautions" to keep the virus from spreading, and would step up its monitoring of humans and poultry and ensure the provision of drugs to treat bird flu.
Djibouti is the first country in east Africa to report the appearance of the H5N1 virus in either birds or humans and is only the second country in Africa to report a human case, after Egypt with five human fatalities from the virus there.
East Africa at risk
Health experts have warned that east Africa was at particular risk for the spread of the virus because it hosts large numbers of migratory birds thought to be carriers, but suspected outbreaks reported after mass bird deaths in countries such as Ethiopia, Eritrea and Kenya have all proved negative to date.
Epidemiologists say the deadly H5N1 viral strain requires very close contact to jump the species barrier. Tens of millions of infected birds have passed the virus on to a total of 206 people in two and a half years. Of these known cases, confirmed by the WHO, more than half have died.
Health officials fear bird flu could turn into a pandemic, if it mutates into a strain easily transmitted between humans.