Lydiate, last season's Six Nations player of the tournament, has been sidelined since October due to a serious ankle injury. He missed Wales' autumn Test series and their successful Six Nations title defence, which culminated in a record 30-3 victory over England last Saturday.
But Lydiate will pack down in Newport Gwent Dragons' back-row for their RaboDirect PRO12 clash against the Ospreys in Swansea.
British and Irish Lions head coach Warren Gatland will be among those eagerly monitoring his progress, with Lydiate thought to be strongly on course for a place in Gatland's squad to tour Australia this summer.
A number of Wales' Six Nations heroes will make an immediate return to domestic action on Friday.
Andrew Coombs joins Lydiate in the Dragons pack, with Toby Faletau on the bench, while the Ospreys' starting XV features fly-half Dan Biggar, hooker Richard Hibbard, prop Adam Jones, locks Alun-Wyn Jones and Ian Evans, plus flanker Justin Tipuric.
"It's great to welcome home our international boys after they did so well in the Six Nations," Ospreys head coach Steve Tandy said. "Last season, they came back to us off the back of a Grand Slam and provided the impetus to build on the work done by the core group while they were away that allowed us to kick on and win the league.
"Having won the Six Nations again thanks to a great victory against England, we will be looking for the boys to have a similar impact this time.
"We've got a lot of work still to do if we are going to secure a place in the top four, but what is really pleasing is the attitude of the boys coming back.
"I spoke to them all after Saturday, and every one of them wanted to be involved in this game. They couldn't wait to get back to their region with their team-mates and roll their sleeves up for the cause."
- Sports & Recreation
- Newport Gwent Dragons
- Warren Gatland