Ole Gunnar Solskjaer suggested Manchester United require years of rebuilding work to reach the standard of Barcelona after their Champions League exit.
It is the heaviest defeat over two legs United have suffered in European competition and means they have now gone eight years without progressing beyond this stage of the tournament.
The defeat is also their fifth in seven games in all competitions and their fourth in a row away from home - the first time they have endured such a run since 1999, when Solskjaer played for the club.
Speaking at a news conference after the match, Solskjaer acknowledged that his side are a long way off the quality of the continent's elite.
"We did well to get here and we could see the difference between the two teams - their quality of finishing was absolutely outstanding," he said.
"We started well, in the first 15 minutes you thought, 'we've got something here' and then in four minutes they scored two goals. But the attitude was right - we got out there, we knew we were fighting against a good team.
"We know there is work to be done. I've said all along that this isn't going to change overnight. The next few years are going to be massive for us to get to the level Barcelona and those teams are at."
The optimism around Solskjaer's return to Old Trafford helped push United back into top-four contention in the Premier League and saw them knock out Paris Saint-Germain in Europe, but they are now facing a battle to claim a coveted Champions League qualifying spot with five games remaining.
Solskjaer, though, insists he is optimistic about the club's future.
"We're on with the job and we've spoken to the players as well," he said. "We need to get the best out of each other and create an environment of top, top, top-class, world-class attitude every day, because I know I've got good players to work.
"We've really, really done well to get to the quarters and challenge for the top four, but we've got a rebuilding job. It starts with the coaches and one or two additions [to the squad] will happen in the summer."
Solskjaer was left to rue the devastating impact of Messi, who scored twice in four minutes in the first half, the second of them seeing David de Gea allow a shot to squirm beneath him.
"He's an exceptional talent," Solskjaer said. "Him and Cristiano [Ronaldo] have been the best players in the world in the last decade. He showed why we think that, why he's won so many titles. You can prepare all you like but if you give him space and time around the goal, he's going to create chances and score goals.
"When you prepare, you can do every tactical tweak but if he gets the ball in and around the box he will always be decisive and unfortunately for us he was the winner for them."
On De Gea's error, the Norwegian added: "It's unfortunate with goalkeepers - when you make an error, it'll get highlighted, and that'll be remembered tonight. He's made some fantastic saves as well. Sometimes it happens. That's football."