"Important projects await us, which we responsibly started without thinking that occasional decisions could put them into question."
Prodi's centre-left government, which comprises far left communists and centrist Catholics, will face the confidence vote in the chamber of deputies on Wednesday.
Clemente Mastella, a key ally in Prodi's government, resigned as justice minister last week and on Monday said his Udeur party would oppose Prodi in a vote of confidence.
Mastella resigned after being named in a corruption probe along with his wife.
He claims the corruption investigation was an effort to discredit him for his efforts to reform Italy's judiciary.
"The experiment with the centre-left is over," he said, after his party's withdrawal from the coalition.
The withdrawal of Udeur, which holds three votes in the senate, has grim implications for Prodi in an upper house vote, given that his coalition now has a two-seat deficit in that chamber.
To survive the senate vote, Prodi would need the support of some of the seven left-leaning senators-for-life, who have cast crucial votes on several occasions.
The centre-right opposition, which is led by Silvio Berlusconi, the former prime minister, has called for Prodi's resignation and for snap elections to be held.
"I think there's no other way than to take this crisis into account," Berlusconi said.
Should Prodi resign, Giorgio Napolitano, Italy's president, could dissolve parliament and call new elections.
Alternatively, he could ask Prodi to stay on as a caretaker prime minister, pending a permanent replacement.
The Prodi government fell briefly in February last year but was reinstated after a vote of confidence in the senate.