INDIANAPOLIS — Sunday's season opener is going to be different for Peyton Manning.

He's playing in a new building, will take snaps from a new center and finds himself behind two new guards. The two-time league MVP can handle all those changes.

It's the other stuff he can't answer yet.

For the first time in 11 NFL seasons, Manning enters a regular-season game without having thrown a single preseason pass and with doubters suggesting he might look rusty Sunday against the Chicago Bears. The perennial Pro Bowler struggles to explain his own expectations.

"I keep using the term unchartered territory, and that's what it's been like for me," Manning said Wednesday before practice. "I hope to just get in the flow of things and go."

Manning's quarterback colleagues probably wish it was that simple.

Then again, Manning is not your typical NFL quarterback. The two-time league MVP has rewritten the preparation manual with his hours-long film sessions, meticulous attention to detail and desire to take every possible snap in practice.

The result: 160 consecutive regular-season starts, eight playoff appearances in 10 years, one Super Bowl ring, five straight seasons with at least 12 wins and, amazingly, 21 consecutive victories in September and October.

He's been a model of consistency.

But Manning has never endured anything like this.

He had surgery July 14 to remove an infected bursa sac from his left knee, missed all of training camp and didn't return to the practice field until Aug. 26 — the longest absence of his pro or college career. Last Thursday, prior to the Colts' preseason finale against Cincinnati, Manning finally went through his normal pregame routine, and resumed his regular work schedule this week when he had no setbacks with the knee.

Now that it appears Manning has finally ended the speculation about missing the opener, doubters have begun a new line of questioning hinging on his effectiveness with such little time to prepare.

"I think when you're a veteran it doesn't hurt you as much as it might hurt some players," Bears coach Lovie Smith said in a conference call with Indianapolis reporters. "But at the same time there is a reason you have training camp. I think every time you practice, you get better. So it has to hurt a little."

Manning's teammates don't seem worried.

Tight end Dallas Clark said he's not "too concerned" and was just glad to have him back. And others contend that Manning is such a workaholic he'll be ready to go no matter what.

Without Manning, though, the Colts' offense didn't look like itself. The starting unit, led by Jim Sorgi, Jared Lorenzen and Quinn Gray, failed to score a touchdown in five preseason games.

Fortunately, the Colts have been through this before.

Although Indy is just 3-15 in preseason games dating to 2005, the Colts have responded when the games mattered most. They've opened each of the last three seasons with at least seven straight wins, the first team in league history to achieve that feat.

This time, it could be a little trickier even with Manning in the lineup.

Jeff Saturday, a three-time Pro Bowl center, will miss Sunday's game after injuring a ligament in his right knee Aug. 24. Saturday has started all but two games since 2000, including 51 in a row.

His likely replacement, rookie Jamey Richard, a sixth-round pick in April's draft, has been working extensively with Manning over the past few days.

"The No. 1 thing on any play is getting the snap, so you put a little more emphasis on that," Manning said. "But I think we'll be OK in that regard."

Incumbent starting guard Ryan Lilja has not fully recovered from offseason knee surgery and will miss the first six weeks after being placed on the physically unable to perform list Saturday. Mike Pollak, Indy's second-round draft pick who was expected to win the vacant job at right guard, also figures to sit out.

The absences mean Indianapolis will probably put three-year veteran Charlie Johnson, who challenged Pollak for one starting job during training camp, at one spot, and Dan Federkeil, who will make his first NFL start, at the other.

All they have to do is keep Manning on his feet against a defense that traditionally ranks among the league's best.

The bigger questions are about Manning's ability to take hits, dodge pass rushers and get his timing down with receivers. Manning hopes to provide the remaining answers Sunday night.

"For me, it's my first game in a long time," he said. "I think the sooner we can get some normalcy back, in terms of let's go play the game, get first downs and convert third downs, the better it will be for this team."