Lackey, who was 49-32 with a 3.72 earned run average in 112 starts over eight seasons with the Angels, allowed one run on two hits against the Angels on May 5 at Fenway Park.
"I had a lot of good years [in Anaheim] and lot of fun here, and I really enjoyed playing here," said Lackey, who signed a five-year, $82.5 million deal with the Red Sox this past offseason. "I won a lot of games in this stadium, so it'll be comfortable once I get out there. I'm not sure whats going to happen. We'll find out."
Lackey has been tremendous in his last two starts but has nothing to show for it, as he has not earned a decision in either outing despite allowing just two earned runs in 15 innings of those outings. Lackey gave up an unearned run and two hits in eight innings to the Seattle Mariners on Thursday, but did not factor in the outcome of his team's 8-6 triumph.
Anaheim, meanwhile, will turn to righty Jered Weaver, who is 9-6 with a 3.22 ERA. Weaver lost for the third time in his last four starts Thursday in Texas, as the Rangers reached him for three runs and seven hits in six innings.
"I was trying to keep us in the game as much as possible," Weaver said. "I wish I could have gotten deeper in the game. Any time you hold that team to three runs in this park [Arlington], you feel like you've done your job."
Weaver is 2-2 with a 3.99 ERA in eight starts against the Red Sox.
The Angels, who lost the opener of this set by a 6-3 score on Monday, hope that things go a little easier for Weaver tonight than it went for Dan Haren in his Anaheim debut on Monday.
Haren (0-1), acquired by Los Angeles on Sunday in a trade with Arizona, exited the game in the fifth inning after taking a Kevin Youkilis line drive off his right forearm. He was diagnosed with a contusion and took the loss, allowing two runs on seven hits to go with eight strikeouts and no walks in 4 2/3 innings.
"It's a little sore and a little tight, but it's not throbbing. It didn't hit the bone," Haren said. "They thought it best to come in and get it checked. The doctor said I should be fine."
David Ortiz homered twice and knocked in three runs to power Boston to the win.
Clay Buchholz (11-6) threw seven innings of one-run ball, yielding just five hits and a walk while fanning seven in his second start since being activated off the disabled list. Jonathan Papelbon nailed down his 23rd save of the season by recording the final four outs.
Victor Martinez (thumb) was in the starting lineup for the first time in a month and drove in a run for Boston, which had lost four of six coming in.
The Red Sox swept a four-game home set over the Angels from May 3-6, but have lost seven of their last 10 in Anaheim.