Pope John Paul II has called on Roman Catholics around the world to pray for his continued strength to lead them.
The Pope's hand is still firmly on the helm of the Church
He was speaking at a special silver jubilee Mass in St Peter's Square before ten of thousands of people.
The 83-year-old, who has Parkinson's disease and arthritis, was slumped in his chair but appeared alert.
Earlier, he delivered a stern message to his bishops reminding them of their duties on issues such as child abuse and forging ties with other religions.
Heads of state and government joined 150 cardinals among the crowd in the square to hear him speak at the 25th anniversary Mass.
In his homily, the Pope said Christ was aware of his human frailty but still encouraged him to bear his responsibilities as Pope, and he asked for Roman Catholics to pray for him.
"I ask you please, very dear brothers and sisters to not interrupt this grand work of love for the successor of Peter," he said in a section of the homily read out for him by an aide.
John Paul II's pontificate has been not only one of the longest in modern times but also in the whole 2,000-year history of the Church.
BBC News Online's correspondent in Rome, Peter Gould, says the Pope has been a dominant figure on the world stage.
The Polish and Italian presidents were at the Mass
As the "universal pastor", he has used air travel and the mass media to spread his message, redefining the papacy for the modern age.
But he has come under strong criticism for his hard line on sexual morality, in particular his opposition to artificial birth control and safe sex which critics say has left millions more exposed to the risk of HIV infection.
Earlier on Thursday, the Pope delivered a strong message to bishops at an audience in the Vatican's Paul VI Hall.
He presented a 192-page exhortation covering issues from child abuse to dialogue with Islam.
After a series of child abuse scandals involving the Church around the world, he called on bishops to act swiftly in cases of "grave lapses and even more of crimes... especially when they involve the church's ministers".
Their duty, he added, was the "reparation of scandal and the restoration of justice and [to do] all that is required for the protection and assistance of victims".
The document also called for dialogue between faiths to bring "peace between peoples", saying the 11 September attacks on America had created "grave new situations of uncertainty and fear".
Travelled equivalent of 30 times around the Earth
Visited 130 different countries and territories
Spent more than three years away from the Vatican
Read more than 19,000 addresses
Held more than 1,100 general audiences at the Vatican - attended by 18 million people
Beatified 1,319 people and canonised 477 saints - more than all previous popes combined
Held talks with more than 1,350 heads of state or
Presided over largest Mass for 4.5 million people in Manila in 1995
It also reminded bishops that to work in "poverty" contributed to making the Church "the home of the poor".
Thursday is only the start of a week of jubilee celebrations.
The Pope will address the cardinals who have gathered to mark the event on Saturday and host a lunch party for them at the Vatican.
Next week he will also present 30 new cardinals with their red hats, bringing up to strength the body which will one day elect his successor.
On Sunday, the Pope will beatify Mother Teresa of Calcutta setting her on the fast track to full sainthood.