Escobar, an 18-game winner in 2007, aggravated shoulder inflammation from September while working out in December. He'd been doing extensive rehab work with the training staff since early February and had been involved in soft-toss for a week when the pain resurfaced on Saturday.
"Everything was going well, and I was just throwing easy when I felt the pain come back," Escobar said. "It's very frustrating, very disappointing. I'll have to wait and see how it goes now. I have to be patient. I can't try to rush it and do too much before I'm ready."
Angels manager Mike Scioscia said it was unclear how long it would be before Escobar is ready to pick up a ball again.
"I don't think it's anything unusual in the rehab scenario to take a step back," Scioscia said. "He was at baby steps. It wasn't anything he was pushing. It's just ... little glitches.
"We'll have to reevaluate him. We're still at baby steps. It's hard to evaluate when he's going to be able to pick things up."
After a strength test showed improvement in the shoulder, Escobar was cleared to start soft-toss on March 15.
"I know you have good days and bad days when you go through this," Escobar said. "I had some good days ... and then a bad one. I'll keep going and do what I can. I want to get back out there when I'm ready and help this team win."
Escobar, 31, experienced shoulder discomfort while throwing before Christmas, then felt more pain two weeks later when he tested it again and notified management. He was summoned to Arizona in early February to begin the rehab process.
Escobar initially had hoped to be back in early May, but that projection would be highly optimistic after this latest setback.
John Lackey, in the early stages of his rehab from a right triceps strain, also will be unavailable in the season's opening month, creating two sizable vacancies in the rotation.
With Scot Shields (forearm stiffness) and Chris Bootcheck (oblique strain) expected to start the season on the disabled list, the Angels will have a reshaped bullpen as well in April.
"We're being tested," Scioscia said. "But we'll be fine."
Scioscia and general manager Tony Reagins have given no indications they're actively seeking arms from other clubs or free agency, maintaining that organizational pitching depth should carry them through until all hands are back on deck.
Lyle Spencer is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.