Mr Hassan says he was flown to Egypt and tortured
Unconfirmed Italian reports named one as Marco Mancini, a senior official at the Sismi intelligence agency.
Arrest warrants for four Americans were also issued, adding to 22 earlier ones.
Italy's previous government denied any role in the seizing of Egyptian Muslim cleric Osama Mustafa Hassan, who says he was taken to Egypt and tortured.
The two arrested men are the first Italians to be linked to the investigation. One is said to be in custody; the other under house arrest.
Mr Mancini is a former head of the anti-terrorist division of the Italian secret service. He has taken part in negotiations to free Italian hostages kidnapped in Iraq.
Kidnap claims
Mr Hassan, also known as Abu Omar, is believed to have been abducted from a Milan street on 17 February 2003, and flown out of the country from Aviano air base north of Venice.
The cleric, who had been granted refugee status in Italy, was already under investigation by Italian officers as part of a terrorism inquiry.
Milan prosecutors probing the kidnap case believe Mr Hassan was snatched by the CIA and taken to Aviano for interrogation, before being flown on to Cairo via Ramstein air base in Germany.
He is still being held in a jail in Egypt, but did make contact with his family and friends during a brief release. A friend who spoke to him said he had suffered electric shocks and other severe torture.
Wanted Americans
The Milan prosecutors' office statement said three of the Americans involved in the fresh arrest warrants were CIA agents, while the fourth worked at the Aviano base.
The US authorities have refused to co-operate with the Italian justice ministry in the 22 earlier arrest warrants, and Italy's Justice Minister Roberto Castelli has refused to pass on to the US a request to extradite them.
Prosecutors tracked the suspects down using mobile phone records, hotel bills and other sources.
Washington acknowledges that it has transferred terror suspects between countries as part of its policy of "extraordinary rendition" - but denies handing them over for the purpose of torture.
Marco Mancini, a director of a division of the Italian SISMI military intelligence agency has been arrested in Milan over his role in the alleged kidnapping of an Egyptian terrorist suspect by agents of the United States' Central Intelligence Agency (CIA) in what is believed to be an instance of Extraordinary Rendition.

Hassan Mustafa Osama Nasr, also known as Abu Omar, is an Egyptian cleric living in Italy who was abducted,  allegedly by covert agents of the CIA on February 17, 2003 from Milan and flown to Egypt, where he says he was tortured. 

Italian investigators suspected that Nasr had links with Al Qaeda and say that they were investigating him when he was abducted. 

In June 2005, Italian judge Guido Salvini issued a warrant for the arrest of 22 persons said to be agents or operatives of the CIA over the kidnapping.