Chris Czekaj - who was named in the Wales Under 21 Six Nations squad yesterday - will start on the wing, with Jonah Lomu retaining his place in the side on the opposite wing.
Cardiff Blues Director of Coaching Dai Young said "We have made several changes to the team for this Friday's match against the Edinburgh Gunners due to the unacceptable performance against the Leeds Tykes last Sunday.
"We are looking for a reaction from the players and if I was totally honest if we had more options we would have made more changes."
Meanwhile Edinburgh have made 11 changes from the side who were comprehensively beaten by London Wasps in the Heineken Cup last weekend.
The Gunners completed the league double over the Blues last season, winning 17-12 at the Arms Park last January.
"We've made quite a few changes but it's exciting," said Edinburgh coach Todd Blackadder.
"There are some challenges ahead and it¿ll be great to see Nick and Dave start this match for the team.
"Rory (Lawson) will lead the side very well I'm sure and there is a lot to play for."
Nick Macleod, Chris Czekaj, Jamie Robinson, Dafydd Hewitt, Jonah Lomu, Lee Thomas, Ryan Powell, Xavier Rush (c), Robin Sowden-Taylor, Maama Molitika, James Goode, Craig Quinnell, Gethin Jenkins, Duane Goodfield, John Yapp
Ben Evans, Ross Johnson, Bradley Davies, Mark Lewis, Mike Phillips, Craig Morgan, Marc Stcherbina
Nic De Luca; Francisco Leonelli, Phil Godman, Matt Dey, Simon Webster; Duncan Hodge, Rory Lawson (capt); Allan Jacobsen, Andrew Kelly, Alasdair Dickinson, Alasdair Strokosch, Dave Duley, Matt Mustchin, Simon Cross, David Callam.
Replacements: Kyle Traynor, Craig Smith, Ross Rennie, Alan MacDonald, Ander Monro, Peter Jorgensen, Mike Pyke.
Tickets are on sale from the Ticket Office - call 029 2030 2030 or visit in person - open until 5pm midweek and later on the day of the game.