Speaking as chairman of the African Union (AU) at a government-sponsored public celebration at Johannesburg stadium, Mbeki urged all Africans to work hard to eradicate the causes of conflict in the continent, especially "the demon of tribalism".
He asked people look beyond the different language and ethnic barriers.
"Tutsi and Hutu are African ... Ndebele and Shona are African... Zulu and Sotho are African. We cannot afford the slaughter of one African by another anywhere on our continent," he said.
He said the purpose of Africa Day was to celebrate 40-years of unity and solidarity in the struggle against colonialism and apartheid.
The day marks the 40th anniversary of the founding of the Organisation of African Unity.
"Just as we have defeated colonialism and apartheid, so shall we banish from our lives the terrible life of poverty and underdevelopment".
He said the New Partnership for Africa's Development – the framework for much of the AU's plans - would prove that the time for Africa's development was now. "We will succeed because we have an abiding faith in the ability of the masses of our people to affect change. These masses are the real agents of change".
At the start of the proceedings South African National Defence Force, soldiers fired a 21-gun salute and pigeons were released into the air.
As the crowd inside the stadium enjoyed a taste of entertainment in truly African style provided by tribal dancers and top South African jazz, gospel and pop stars, the crowd outside were baying to be let in.
The 20 000-seater stadium was already full when some 2 000 more people arrived and demanded to be let in.
At times, the situation was tense with bottles thrown and batons wielded. At one stage, the police fired a stun grenade into the crowd to move the people away from a gate on the western side of the stadium.
At other times the crowd and the police relaxed long enough to enjoy brief glimpses of the entertainment inside and the sight of half a dozen parachutists dropping into the stadium as well as a fly-over by military helicopters.
Inside or outside, it was the masses rather than the political elite that Mbeki was addressing.
"We will succeed because we have an abiding faith in the ability of the masses of our people to affect change. These masses, occupying their different stations in life are the real agents of change - the workers, the women, the children, the artists, the business people”.
Among the dignitaries who attended the function were Mali's President Amadou Toumani Toure, AU interim secretary general Amara Essy and diplomats.
Deputy-president Jacob Zuma and several South African cabinet ministers, including Education Minister Kader Asmal, Environmental and Tourism Minister Valli Moosa and Foreign Affairs Minister Nkosazana Dlamini-Zuma were also there.
Besides Mbeki, Toure was the only head-of-state from the AU's 53 member states to attend the celebrations. – Sapa.
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