Rendon has been on the disabled list all season recovering from knee and oblique injuries.
Asche was sent to the minors on May 11 to work in the outfield. He hit .295 with one home run, three doubles, three RBI, six walks and nine strikeouts in 15 games. He played all 15 games in left field.
All three of the hits for Middlebrooks were singles. He drove in one run and scored a run during the game.
Middlebrooks is 9 for 22 with two home runs and five RBI in his last five games. During that time, he has raised his batting average from .211 to .240.
Middlebrooks opened up the scoring with an RBI double in the second inning before adding a two-run homer in the fourth to give his team a 3-1 lead. It's the third two-hit performance in four games for Middlebrooks, who owns a .226/.260/.397 line with six home runs and 17 RBI in 146 at-bats.
Rendon, who is working his way back from an oblqiue strain, took a couple of at-bats and played in the field for all of the innings after his second at-bat.
"It's important. It helps you get your legs under you," Williams said. "…there's no way to simulate that other than to play. He felt good. His legs felt good."
Rendon is scheduled to get the day off on Thursday and the team will re-evaluate his health.
The Dodgers traded Uribe to Atlanta for Alberto Callaspo on Tuesday.
Left fielder Johnny Gomes will hit seventh and Andrelton Simmons will bat eighth.
Padres manager Bud Black said Middlebrooks could "potentially" see more action at shortstop depending on the matchups he will face.
Coming into Tuesday's game against the Angels, Middlebrooks had made just one start at shortstop while making a team-high 34 at third base.
He also had his eighth double on Wednesday, as he finished 2 for 3 with two RBI and one walk. Frazier is batting .281 with one triple, four doubles, seven home runs and 12 RBI in 24 May games.
Arenado finished the game 2 for 4 with one strikeout. He has homered three times in his last four games.
He is 9 for 16 (.563) with one triple, three home runs and 10 RBI in his last four games after batting .177 (11 for 62) with one home run, three doubles and four RBI in his previous 17 games.
Uribe was part of a crowded infield in Los Angeles and was hitting .247 with six RBI in 81 at-bats this season. Withrow is yet to pitch this season after posting a 2.95 ERA in 21 1/3 innings of work in 2014.