The ride marked his return to grand prix action after stand-in rides for the Interwetten Honda MotoGP team, then the exit of the Scot Moto2 team to which he had planned to return.
The Sammarinese had been second behind JiR regular Simone Corsi for the middle part of the session, with the pair then bumped down the order in the final 10 minutes.
But de Angelis retaliated in style by taking the top spot with one and a half minutes remaining and finished the session 0.147 seconds ahead of Julian Simon's Aspar Suter.
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Early-season title leader Shoya Tomizawa was third for Technomag-CIP, with another Suter of Claudio Corti in fourth place.
Title leader Toni Elias, riding in white and red San Carlo colours this weekend - the same as the Gresini MotoGP team - was fifth and the leading Moriwaki entry.
Mattia Pasini, who split from JiR earlier in the year, is making his debut for the Italtrans S.T.R. squad this weekend. The Italian was a promising sixth on Friday.
Hector Faubel enjoyed a tow from Elias on his way to a late seventh for Marc VDS, just 0.5s from de Angelis, with Corti's team-mate Jules Cluzel eighth.
Corsi slipped all the way back to ninth after technical troubles.
Fimmco Speed Up riders Gabor Talmacsi and title contender Andrea Iannone were ninth and tenth.
Niccolo Canepa, who had been team-mate to de Angelis at Scot, is also back for Misano, riding a Bimota for the M Racing team. The 2009 Pramac Ducati MotoGP rider finished the session in 35th.
In a further development, Joan Olive seems to have switched to an FTR chassis for this weekend, while Jack & Jones by A. Banderas team-mate Kenny Noyes is still running the Promoharris. Olive was 34th and Noyes 38th out of the 39 riders.
Friday practice - Misano:
1. de Angelis (MotoBI) 1m 40.064s
2. Simon (Suter) +0.147s
3. Tomizawa (Suter) +0.310s
4. Corti (Suter) +0.353s
5. Elias (Moriwaki) +0.424s
6. Pasini (Suter) +0.429s
7. Faubel (Suter) +0.500s
8. Cluzel (Suter) +0.522s
9. Corsi (Motobi) +0.543s
10. Talmacsi (Speed Up) +0.650s
12. Redding (Suter) +0.704s
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