Milan's 4-2 defeat of Slavia Prague followed a slim league victory over eight-man Lazio, while their Tuscan counterparts suffered a first loss in seven last time out.
Match preview
Having previously swatted aside Rennes in the knockout-round playoffs, Milan kicked off their Europa League last-16 tie on Thursday evening, as Czech side Slavia Prague paid a visit to Italy's second city.
With their visitors reduced to 10 men before the break, Stefano Pioli's men marched into a 3-1 lead by half time, and despite spirited Slavia pulling one back, Christian Pulisic struck again in the closing stages to put his team in command ahead of next week's second leg.
With a possible European quarter-final to come, the Rossoneri still have some hope of securing silverware this season, as the Scudetto is surely out of reach: they trail city rivals Inter Milan by 16 points in the Serie A standings, and are one point behind second-placed Juventus.
Nonetheless, only Inter have collected more points and scored more goals than Pioli's side since December, thanks to a full squad effort: Pulisic, Rafael Leao and top scorer Olivier Giroud have been backed by an able supporting cast, including Giroud's deputy Luka Jovic and Swiss striker Noah Okafor.
The latter's late winner against Lazio in Milan's first March fixture brought their goalscoring run to some 23 matches, and upcoming games against Empoli and Hellas Verona may provide the chance to extend that sequence even further.
With victory this weekend, Pioli would surpass 350 points as Milan boss, becoming just the second manager to reach such a milestone this century, after club legend Carlo Ancelotti (557). However, rumours persist that this may be his final campaign in charge.
Ahead of their latest trip to San Siro, Empoli have won just once in their last 14 league meetings with Milan - and not for almost seven years.
A recent resurgence has helped the Tuscan club climb away from Serie A's drop zone, but they remain in serious danger of demotion despite putting together a six-game streak without defeat under new boss Davide Nicola.
Although they were beaten at home by relegation rivals Cagliari last week, Empoli's first eight matches in the second half of this season have brought 12 points, which is just one fewer than the entire first half of the current campaign.
The Azzurri's home record remains the second-worst throughout Serie A, but picking up points on their travels has become a happy habit of late: after a run of five away games without victory, they have recently seen off Salernitana and Sassuolo - two more competitors for top-flight survival.
The last time Empoli won three consecutive away games at this level was back in 2016, but pulling off such a feat now would be quite an achievement given Milan's goalscoring form since the start of the year, when the Rossoneri cruised to a 3-0 win at Stadio Castellani.
AC Milan Serie A form:
D
W
W
L
D
W
AC Milan form (all competitions):
W
L
L
D
W
W
Empoli Serie A form:
D
D
W
D
W
L
Team News
Due to one-match bans for both Rafael Leao and Alessandro Florenzi, Milan will make at least two changes to the team that started on Thursday - most probably more, as hinted by Stefano Pioli.
Noah Okafor and Samu Chukwueze are competing to replace Leao, and club captain Davide Calabria should come in for Florenzi at right-back; meanwhile, veteran duo Olivier Giroud and Simon Kjaer could be rested.
Giroud scored in January's reverse fixture, and has 12 league goals to his name this term - just one fewer than last season's final total - but Luka Jovic may be asked to deputise up front.
Having scored only eight times in 67 Serie A matches for Milan between 2012 and 2017, M'Baye Niang has been directly involved in four goals from as many games since joining Empoli earlier this year: three converted penalties and one assist.
He will vie with Alberto Cerri and another ex-Milan striker, Mattia Destro, to lead the Azzurri's front line this weekend.
Alberto Grassi and Francesco Caputo are both set to miss out through injury, but Szymon Zurkowski should overcome an ankle problem to start in midfield.
AC Milan possible starting lineup:
Maignan; Calabria, Thiaw, Gabbia, Hernandez; Bennacer, Reijnders; Pulisic, Loftus-Cheek, Okafor; Jovic
Empoli possible starting lineup:
Caprile; Ismajli, Walukiewicz, Luperto; Gyasi, Maleh, Marin, Cacace; Zurkowski, Cambiaghi; Niang