The five-year-old is aiming for an unprecedented hat-trick of wins in the prestigious Tokyo race, which will run for the 34th time.
Gentildonna is a six-time Group 1 winner and connections will hope their horse can extend the run of local successes - currently at eight.
Alkaased was the last foreign horse to claim the race in 2005.
Ryan Moore is on board the two-time winner and is in great form after riding victories in the Cox Plate and Melbourne Cup recently.
Gentildonna did not win its last start, though, running second in the Tenno Sho (Autumn), but has triumphed in all her three starts over 2,400m at the track.
"She's been working at a steady rate since the Tenno Sho, and she's been lively ever since," Ishizaka said.
"The good thing for us is that we'll be racing at Tokyo again.
"Our goal is to win a third consecutive Japan Cup and I hope we attain a good result here."
Gentildonna has drawn gate three.
The horse who beat Gentildonna at the Tenno Sho (Autumn) - Spielberg - is in the field and starts from gate 15, while Harp Star - who will go from sixth - is also given an excellent chance.
Questions over the ride in its sixth-placed finish at the Arc de Triomphe have seen punters happy to give Harp Star a second chance.
The world's highest-rated racehorse, Just A Way, is also in the field and has won twice in Tokyo.
And foreign horses, Trading Leather and Ivanhowe are also given a chance.