The Rossoneri have yet to lose in Serie A under the Dutchman but Napoli are third in the standings and have lost just once at the San Paolo stadium this season.
"It's going to be a difficult game in Naples," AC Milan goalkeeper Christian Abbiati said to www.acmilan.com. "It's a big test for us to see where we are at.
"The dismissal of (coach) Massimiliano Allegri (back in January) was a big failure for us, the players.
"Seedorf's impact has been great.
"He has come in and changed things around.
"He has brought in some new ideas, and hopefully they will make a difference on the pitch."
Last weekend's 1-1 draw against Torino extended Milan's unbeaten run to three league games and lifted the Rossoneri to 10th place, six points adrift of Hellas Verona, who hold the last Europa League qualifying spot.
The Rossoneri will be bolstered by the return of the team's top scorer Mario Balotelli from suspension and will be hoping to have midfielder Kaka available, with the Brazil international doubtful with the flu.
Rivals Napoli go into the encounter looking to end a disappointing week on a positive note.
The Azzurri surprisingly lost 3-0 at Atalanta last weekend before falling 3-2 at Roma in Wednesday's Coppa Italia semi-final first leg.
Napoli have collected just two points in their last three Serie A matches but are still three points clear of nearest rivals Fiorentina.
"The time has come to return to win," Napoli midfielder Marek Hamsik said. "Two points in three games is simply not good enough for us, we have to do better."
Hamsik knows his side will have to be on guard against a reinvigorated Milan, who will be looking to avenge their 2-1 defeat at home to Napoli earlier this season.
"Milan are climbing up in the standings," he said. "They have changed coach and we know it will not be an easy game.
"We played really well against them at the San Siro but every game is different."
The hosts will be without injured right-back Anthony Reveillere.