Senator Collins - who first entered parliament in 1995 - says now is the right time for her to move on.

"I have been grappling with challenging family health issues for several years and I am keen to pursue a better work and family balance," she said in a statement on Wednesday.

The senator briefly served as minister for mental health and ageing in 2013, during Kevin Rudd's short-lived return to the Labor leadership.

She has also served as deputy leader of the government and manager of government business in the Senate.

But Senator Collins said her time as assistant minister for school education and workplace relations between 2010 and 2013 - the Julia Gillard years - was a "real highlight" of her parliamentary career.

"I was proud to play a key role in the Gonski school education reforms as well as the introduction of the Fair Work Act which buried the Howard government's unfair and unpopular WorkChoices legislation," she said.

The senator also stressed her enthusiasm for Bill Shorten's leadership, saying it has been "energising and rewarding" to contribute to his team.

Mr Shorten has thanked the senator, noting she has helped deliver stability in opposition and been pivotal to the party's outreach to multicultural and faith communities.

"Jacinta has won a reputation as a smart, fearless and determined parliamentarian," the Labor leader said in a statement.

"After more than two decades in Canberra, Jacinta has certainly earned the right to spend more time with her family."

Senate colleague Penny Wong said the upper house would be poorer for her departure.

"Senator Collins has been a determined and principled representative of Victoria in the Senate across two decades," she said.

Australian Associated Press