The Pope has praised the efforts of all sides involved in the "progress towards achieving peace and reconciliation in Northern Ireland".
The new UK ambassador presented his credentials at the Vatican
He said the most visible sign of the growth of mutual trust was the recent decommissioning of weapons by the IRA.
Pope Benedict XVI was speaking as he accepted the credentials of new UK Vatican ambassador Francis Campbell.
The 35-year-old from County Down is the first Catholic appointed UK ambassador to the Vatican since the Reformation.
Pope Benedict also said the wounds resulting from four centuries of separation between the Anglican Church and Rome could not be healed without determined efforts, perseverance and prayer.
He added that the search for unity among separated Christians was not simply a matter of concern to Christian communities themselves.
He said it was an essential part of overcoming divisions between nations.
On Friday, the Pontiff accepted the credentials of Mr Campbell, who is the first Northern Irish Catholic to hold a UK ambassadorial post since the Republic of Ireland gained independence in 1921.
BBC correspondent David Willey said heads of the diplomatic mission in Rome were normally at the end of their careers and that Mr Campbell was "a career diplomat of a new breed".
He "has the ear of Downing Street" as a former adviser on European affairs to Prime Minister Tony Blair, David Willey said.
The job was advertised in a newspaper in July - the first time an ambassadorial post had been put out to open competition in an advert.
The previous ambassador, Kathryn Colvin, left in September after three years at the Vatican.