At a morning news conference at the Montreal Science Centre, Couillard was flanked by several high-profile MNAs including Yves Bolduc who succeeded him in the health portfolio when he left politics four years ago.
"I feel the need to serve. I could feel this big wave of desire in me to serve again," said Couillard."I believe I'm coming back richer in knowledge, richer with experience and today, I am ready to return to public service."
Couillard said as Liberal leader he would focus on economic development, paying down the debt, and lowering taxes.
He also made a special appeal to anglophones.
"We've all received a signal from this community that they don't feel they are desired or part of this community. They just want their voices to be heard," he said.
"I want to hear your voices and encourage you to become actively involved in this leadership race."
The 55-year-old former neurosurgeon was elected as member of the National Assembly in 2003 and represented the Mont-Royal and Jean-Talon ridings during his time in office.
Couillard held the health portfolio until 2008, when he left politics to join Persistence Capital Partners (PCP), a private equity fund that focuses on health services.
He was criticized in some quarters for negotiating the terms of his private-sector employment while he was still a cabinet minister.
Couillard addressed that head on Wednesday, saying there was never any conflict of interest but admitting he could have explained his decision better.
PQ Health Minister Réjean Hébert told reporters in Quebec City that he hopes Couillard will clarify what happened.
"The exit of Philippe Couillard was problematic because he jumped into the private sector immediately after the role he had as a minister and I think there is a problem there and he will respond to that I hope in the next few days," said Hébert.
Former cabinet colleagues Sam Hamad and Kathleen Weil will direct Couillard's campaign.
Three candidates now in race
Couillard is the third candidate to enter the race to replace Jean Charest as leader of the Liberal Party.
Former finance minister Raymond Bachand and former transport minister Pierre Moreau both announced their intentions in the last week.
Charest stepped away from his role after being defeated in the provincial election on Sept. 4 by Parti Québécois leader Pauline Marois.
The last race for the party's leadership took place in 1983.