Mary Harney has resigned as Minister for Health and it is expected changes in the cabinet will be announced by the Taoiseach in the next few days.
Ms Harney confirmed she would not stand in the forthcoming general election, but also made the surprise announcement that she would step down as Minister.
Her resignation follows that of Minister for Foreign Affairs Micheál Martin last night after the vote of confidence in Taoiseach Brian Cowen as leader of Fianna Fáil.
Ms Harney told RTÉ News she did not believe it was appropriate for someone who was not running in the election to continue to serve in Cabinet.
She said she had informed the Taoiseach of her decision last week, but that he asked her to hold off on the announcement.
Ms Harney said she assumed that her resignation would be accepted, and that as the Taoiseach already had to fill one vacancy at Cabinet, he would fill her position at the same time.
A TD for Dublin Mid West, Ms Harney had served as minister for health since 2004.
She was a founder member of the Progressive Democrats along with Desmond O'Malley in 1985 and became leader of the party in 1993.
As leader of the PDs, she was tánaiste from June 1997 to September 2006. She stepped down as PD leader at that time and was replaced by Michael McDowell.
After his defeat in the 2007 general election, Ms Harney stepped back in as acting party leader.
She also served as minister for enterprise from 1997 to 2004 and minister of state for the Department of the Environment from 1989 to 1992. An achievement often cited from her role in environmental protection was the banning of bituminous coal in Dublin in 1990.
A native of Ballinasloe, Co Galway, she was first elected to the Dáil in 1981. She was the youngest ever member of the Seanad when nominated by then taoiseach Jack Lynch in 1977.