Richard Lochhead is stepping down from the Scottish Cabinet.
The rural affairs secretary, who has been in the cabinet for nine years, said in a letter to Nicola Sturgeon that he was stepping down because he wants to 'change the priorities' in his life.
His wife revealed that she had been diagnosed with breast cancer last year.
Mr Lochhead's decision comes as Nicola Sturgeon prepares to reshuffle her cabinet.
Mr Lochhead tweeted: "Thank you to great people across Scotland I worked with. Hugely rewarding. Sometimes tough. Always absolute privilege."
Thank u to great people across Scotland I worked with. Hugely rewarding. Sometimes tough. Always absolute privilege. https://t.co/HKjp6iFMlP
— Richard Lochhead (@RichardLochhead) May 18, 2016
There had been speculation that Mr Lochhead could be moved from rural affairs in the Cabinet reshuffle following a controversy over a delay in the transfer of Common Agricultural Policy payments to farmers.
Liberal Democrat MSP Mike Rumbles had said that he would call for a vote of confidence on Mr Lochhead if he remained rural affairs minister.
Read more: Lochhead to face farmers wrath over delayed BPS payments
The Moray MSP said that it had been an absolute privilege to serve in the cabinet in a letter to Nicola Sturgeon.
He wrote: "I am very proud of the SNP Government's record and what we have been able to achieve together in recent years including many achievements in my own portfolio.
"I will take away with me many precious memories of the people I have met across Scotland during my time as Cabinet Secretary, and of the people I have worked with, and of the many often historic moments I shared with the team during my term in office."
It has been reported that the First Minister has told Mr Lochhead he could be welcomed back to Government in the future.
In a letter to Mr Lochhead, Ms Sturgeon wrote: "You have always been a robust and articulate advocate and defender of our farmers and fishermen in Europe, despite the challenges posed by the fact that Scotland's Ministers are all too frequently locked out of key discussions.
"I know that you will continue to be a first class representative for your constituents in Moray in the years ahead."
Read more: Ruth Davidson calls for inquiry into EU farmer payment delays
Mr Lochhead has been cabinet secretary for rural affairs since 2007.
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