A World Cup winner with England in 2003 and a finalist in Paris four years later, Regan won 46 caps for his country.
The 37-year-old Bristol hooker won the Heineken Cup with Bath in 1998 and the Powergen Cup with both Bath and Leeds later in his career.
Regan, who is considering a number of business-related opportunities after his retirement, will see out the 2008/09 season at the Memorial Ground before continuing to take his RFU coaching badges.
"I can truly say that I have loved every single minute of my rugby career," said Regan, who has made more than 400 first-class appearances and has represented the Barbarians and a World XV on eight occasions.
" Any other sports professional will understand how difficult it is to make the decision to retire, and this announcement has not been an easy thought process.
"I realise I have lived the dream of any kid who has picked up a rugby ball and wanted to wear the red rose of England.
"I'm extremely proud of the career I have had and I'd like to thank everyone who I have worked with over the years, from developing through the school and age-group ranks through to the international level and my current employers Bristol.
"I have enjoyed 20 years at the top of the game and have been in regular dialogue with Bristol Rugby since the turn of the year. I may be retiring from playing, but I'm not retiring from being involved in rugby, the world of business and the community in general."