It wasn't until the final 17 minutes that the pack began to respond to Pedrosa's dominance, and even then only Yamaha's Ben Spies was able to make serious inroads.
The Texan improved his own best several times as he established himself a clear second fastest.
He still ended 0.295s down on Pedrosa, with the Spaniard underlining his complete control by shaving another few hundredths off his personal best in the final minutes to end on a 1m39.783s.
Jorge Lorenzo completed the top three courtesy of a late flyer one minute before the flag, but he was unable to get within seven tenths of Pedrosa.
Tech 3 Yamaha's Andrea Dovizioso and Cal Crutchlow were also late improvers. Both set their fastest times as the chequered flag flew, earning fourth and sixth respectively, sandwiching Honda's Casey Stoner.
Satellite Honda riders Alvaro Bautista (Gresini) and Stefan Bradl (LCR) took seventh and eighth ahead of the two works Ducatis, with Nicky Hayden just over one tenth of a second faster than Valentino Rossi.
On the satellite Pramac Ducati Toni Elias took over from Hector Barbera, the Spaniard having fallen heavily and fractured three vertebrae in the opening session. Elias finished down in 17th.
Indianapolis GP FP2 times:
1. Dani Pedrosa, Repsol Honda Team, 1:39.783
2. Ben Spies, Yamaha Factory Racing, +0.295
3. Jorge Lorenzo, Yamaha Factory Racing, +0.719
4. Andrea Dovizioso, Monster Yamaha Tech 3, +0.777
5. Casey Stoner, Repsol Honda Team, +0.840
6. Cal Crutchlow, Monster Yamaha Tech 3, +1.272
7. Alvaro Bautista, San Carlo Honda Gresini, +1.289
8. Stefan Bradl, LCR Honda MotoGP, +1.472
9. Nicky Hayden, Ducati Team, +1.614
10. Valentino Rossi, Ducati Team, +1.746
11. Randy De Puniet, Power Electronics Aspar, +2.072
12. Karol Abraham, Cardion AB Motoracing, +2.496
13. Mattia Pasini, Speed Master, +2.507
- Dani Pedrosa
- Ben Spies