A pair of early goals from Giovanni Simeone, and a late header from Leo Ostigard, settled the match for the hosts as Rangers now turn their attentions in the competition to the final group stage clash with Ajax at Ibrox next season.
Giovanni van Bronckhorst made four changes to his Rangers side from the weekend, with Alfredo Morelos, Scott Wright, James Sands and Ridvan Yilmaz coming into the starting lineup.
Rangers settled on the ball nicely during the initial exchanges, although Napoli threatened in the fifth minute when Tanguy Ndombele fired a cross into Giovanni Simeone, only for the Italian forward to head over.
However, the Italian side took the lead on ten minutes. Giovanni Di Lorenzo threaded a pass inside that found Simeone’s run, with the Argentine controlling before firing into the bottom corner.
Napoli then doubled their lead five minutes as Simeone was once again on the scoresheet, heading home from Mario Rui’s pinpoint delivery from the left-hand side.
Tanguy Ndombele struck the crossbar with an effort from the edge of the penalty area after being teed up by Di Lorenzo in the 21st minute.
Scott Wright threatened with a pull-back on 33 minutes as he latched onto Alfredo Morelos’ through pass, but Napoli were quick to thwart the danger.
McGregor denied Giacomo Raspadori’s header after Matteo Politano dug out a cross on the touchline.
However, Rangers engineered their best moment of the first half in the 40th minute following neat interplay. Ridvan found Morelos inside who played a first time lay-off into Malik Tillman. The American danced inside before unleashing at goal, only for Kim Min-jae to block his goalbound effort.
Morelos raced through on goal on the stroke of half-time, but his finish was well-saved by Alex Meret down to his left.
Van Bronckhorst shuffled his attacking options at the interval by replacing Scott Wright with Fashion Jr.
McGregor was called into action six minutes after the restart, thwarting Simeone’s attempt for a hat-trick after being released by Ndombele.
Stanislav Lobotka was alert at the front post to sniff out Ridvan’s dangerous driven delivery across goal following a positive passage of play involving both Morelos and Ryan Kent.
Morelos similarly threatened just past the hour mark. Ben Davies rose highest to meet James Tavernier’s corner, glancing a header onto the Colombian at the far post whose effort required a heroic block from a Napoli defender.
Kent’s enticing delivery from the left narrowly evaded Morelos in the penalty area minutes later as Rangers enjoyed their most dangerous spell of the evening.
Mario Rui drew a fine stop from McGregor with 11 minutes to play, before Leo Ostigard added Napoli’s third goal on the evening with a header from the resulting corner.
Rangers looked to reduce the arrears late on in the contest, with Fashion Jr. driving forward positively before his effort at goal was blocked. Seconds later, Antonio Colak met Tavernier’s floated delivery from a free-kick but steered his header agonisingly wide.
The full time whistle blew in Naples as Rangers now shift their focus to this weekend’s Scottish Premiership clash with Aberdeen.
NAPOLI: Meret, Di Lorenzo (Zanoli, 85), Kim, Ostigard, Mario Rui, Lobotka (Zielinski, 82), Ndombele, Elmas (Gaetano, 72), Politano (Lozano, 72), Raspadori (Zerbin, 82), Simeone
Subs not used: Boffelli, Idasiak, Jesus, Olivera, Anguissa, Kvaratskhelia, Osimhen.
RANGERS: McGregor, Tavernier, King (Barisic, 75), Davies, Ridvan, Sands, Lundstram, Tillman (Arfield, 66), Wright (Fashion Jr., 45), Morelos (Colak, 66), Kent
Subs not used: McLaughlin, McCrorie, Devine, Allan, Davis, Lowry, Matondo.
REFEREE: Halil Umut Meler
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