In an article inside its Dabiq magazine, IS threatens to "conquer" Rome and "break your crosses".
The front page of the militant's magazine shows the IS flag in St Peter's Square.
The issue urges extremists to declare war on the Christian Church.
Tens of thousands of Christians have already been killed or forced to flee their homes by IS in Iraq and Syria.
In some areas believers were told to pay a tax, leave or face death.
The magazine urges Muslims to kill "every Crusader possible" and says "it is lawful to kidnap the women of the infidels and use them as sex slaves".
"We will conquer your Rome, break your crosses and enslave your women, by the permission of Allah, the Exalted. This is His promise to us; He is glorified and He does not fail in His promise," it said.
Last month, the Vatican stepped up security amid the growing threat from Islamic State attempting attacks in Europe.
