Rees – affectionately known across the rugby world as Smiler - has been out of action since October having taking an enforced period away from the sport to receive medical treatment.
But after being given the all-clear to return to full training last month, the former Wales’ international is set for his first appearance in over five months after being named among the replacements to face high-flying Ulster.
Blues make a total of seven changes to the starting line-up that lost to Ospreys as they hunt a winning finale on home soil this season.
Samoa international centre Isaia Tuifua is called up to join forces with Cory Allen in midfield while Chris Czekaj is named on the wing. Harry Robinson misses the game after picking up an ankle injury against Ospreys.
Scrum half Lewis Jones is handed a starting spot and will combine with Gareth Davies at half back.
Hooker Kristian Dacey and lock Lou Reed, who makes his 100th appearances in the PRO12, are the new faces in the front five.
The final change to the starting line-up sees Macauley Cook named at blindside flanker. Cook will join forces with Josh Navidi and Robin Copeland, who makes his 50th appearance for Blues, in the back row.
Rees, Thomas Davies and James Down are among those given a call-up to the replacements bench.
Coach Dale McIntosh said: “We were not happy with the manner of last week’s performance and we need to make sure we react in the right way. We have to do justice to the jersey, show how much last week hurt and perform in our final home game at the Arms Park.
“We need to be mentally prepared and ready. We say goodbye to the Arms Park for another season and we do not want to end on a sour note.
“Every game is massive to me, you put in a huge effort and the best performance you possible can. But as our last game at the Arms Park we want to put in a big display for our fans.
“Having Matthew (Rees) back is a huge inspiration to us all,” he added. “I am sure he will get a fantastic reception and he is a humble lad who will deal with it and get on with it. But I know how keen he is to get back out on the field and get that Blues jersey on his back.”
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Cardiff Blues: 15 Dan Fish, 14 Alex Cuthbert, 13 Cory Allen, 12 Isaia Tuifua, 11 Chris Czekaj, 10 Gareth Davies, 9 Lewis Jones; 1 Gethin Jenkins (c), 2 Kristian Dacey, 3 Taufa’ao Filise, 4 Lou Reed, 5 Filo Paulo, 6 Macauley Cook, 7 Josh Navidi, 8 Robin Copeland
Replacements: 16 Matthew Rees, 17 Thomas Davies, 18 Scott Andrews, 19 James Down, 20 Ellis Jenkins, 21 Lloyd Williams, 22 Simon Humberstone, 23 Gavin Evans