Regional strongman and Ethiopian Prime Minister Meles Zenawi has died in a foreign hospital, the government says.

Ethiopian Prime Minister Meles Zenawi, a regional strongman in the volatile Horn of Africa who ruled with an iron fist for over two decades, has died in hospital in Brussels, officials say.

Meles, a former rebel who came to power in 1991 after toppling the bloody dictatorship of Mengistu Haile Mariam, set Ethiopia on a path of rapid growth and played a key role in mediating regional conflicts.

He also drew criticism for cracking down on opponents and curtailing human rights.

The 57-year-old had not been seen in public since the G20 summit in Mexico in June.

European Commission spokesman Olivier Bailly said on Tuesday that Meles had died in Brussels, where he had reportedly been hospitalised. The Ethiopian government said only that he had died abroad.

"Prime Minister Meles Zenawi passed away yesterday evening at around midnight," said government spokesman Bereket Simon.

"He has been struggling to be healthy in the last year ... one of the best things about him was that he never considered that he was ill and he was up to the job every time, every day, every evening," he added.

"He had been recuperating well, but suddenly something happened and he had to be rushed to the ICU (intensive care unit) and they couldn't keep him alive."

Deputy Prime Minister Hailemariam Desalegn, 47, will take over interim power.

"According to the Ethiopian constitution the deputy prime minister will have to go to parliament and take the oath, and the government is organising the parliament to be summoned as soon as possible," Bereket said.

Hailemariam, 47, has been deputy prime minister and foreign minister since 2010, and was previously special adviser on social affairs to Meles.

Unlike many core members of the ruling party, he does not hail from the far north of the country but from the Southern Nation, Nationalities and People's Region, the most populous of Ethiopia's nine ethnic regions.

Meles was regularly singled out by rights groups as one of the continent's worst human rights predators, and Amnesty International called on new leaders to "take the opportunity for change" to end his government's "ever-increasing repression".

The rebel Ogaden National Liberation Front - which has been fighting the central government for decades for greater autonomy in the vast south-eastern ethnic Somali region - said it hoped Meles' death "may usher (in) a new era of stability and peace."

Ethiopia has declared a state of national mourning, but has not fixed a date for a funeral, said Bereket, adding that "everything is stable" in the country.

Diplomats and analysts in Addis Ababa say it has not been clear how the government has been run since Meles was reported to have fallen sick in June.

Kenyan Prime Minister Raila Odinga told the BBC that Meles had been "a great leader" but said he also "fears for the stability of Ethiopia upon his death".

"The Ethiopian state is very fragile," he said.

"I don't know if they have sufficiently prepared for his succession ... but one would hope they could contain the various factions within the government so that the transition is smooth."

Meles was credited with Ethiopia's economic boom in the past decade, with economic growth shooting from 3.8 per cent in the 1990s to 10 per cent in 2010.

On paper, his government fostered a policy of ethnic federalism, devolving significant powers to regional, ethnically based authorities, but central control remains firmly in the hands of the ruling party.

His death also leaves a major power gap in the Horn of Africa, with Ethiopia playing a key role in the fortunes of many of its neighbours.

Ethiopian troops invaded Somalia for a second time last year - after a US-backed invasion in 2006 - and Ethiopia is supporting the fight against Somalia's Al-Qaeda-linked Shebab insurgents.

Meles's death could also potentially see changes in the relationship with arch-foe Eritrea, which split from Ethiopian rule in 1993 before the two spiralled into a bitter 1998-2000 border war, in which tens of thousands died.

A peace deal led to a tense standoff, with Meles refusing to pull troops from the border town of Badme, even after an international court ruled the town belonged to Eritrea.

The town has been the source of festering discontent between the two nations ever since.

Meles also played a key role in brokering peace efforts between newly independent South Sudan and its former civil war foe Sudan.