Messi will be looking to collect his second Champions League winners medal when he lines up against United at Wembley on Saturday.
But despite being widely considered as the world's best footballer the Argentina international has never scored on English soil in the Champions League.
In his way stand Sir Alex Ferguson's United, fresh from winning a record 19th English league title and desperate to win Europe's elite club competition for a third time.
With United's Park Ji-sung already declaring: "He (Messi) is one of the best players in the world - everyone knows that and everyone knows one defender can't stop him so we have to defend as a team," the Barcelona ace looks set to have his work cut out this weekend.
Here's a look at how the diminutive Argentina international has done during his previous outings in England.
Chelsea 1 Barcelona 2 - 1st knockout round, 1st leg, February 2006
Chelsea took a second-half lead through a Thiago Motta own goal after full-back Asier Del Horno had seen red for fouling Messi. A John Terry own goal and a late Samuel Eto'o strike gave Barcelona victory. Messi saw a 72nd minute free-kick crash against the crossbar.
Chelsea 1 Barcelona 0 - group stage, October 2006
A fantastic Didier Drogba goal gave Jose Mourinho's Chelsea a vital group stage win. Messi was kept at bay by a smart save from Chelsea goalkeeper Hilario before heading wide when well placed late on.
Liverpool 0 Barcelona 1 - 1st knockout round, 2nd leg, March 2007
Eidur Gudjohnsen's goal was not enough for Barcelona who were eliminated by eventual runners-up Liverpool on away goals. Rafael Benitez set up his side to frustrate the Catalans and that is exactly what happened. Messi was on the periphery for the majority of the game but did provide the assist for Gudjohnsen's strike.
Manchester United 1 Barcelona 0 - semi-final, 2nd leg, April 2008
A close semi-final was decided by a trademark Paul Scholes goal early in the second leg at Old Trafford. Messi starred for Barcelona as they rallied for a pivotal away goal but his slalom-run through the United defence ended in a shot that was well saved by Edwin van der Sar. United went on to lift the trophy after beating Chelsea on penalties in the final.
Chelsea 1 Barcelona 1 - semi-final, 2nd leg, May 2009
Another semi-final against English opponents, but this time Andres Iniesta's injury-time goal saw Barcelona reach the final in Rome. Messi was ineffectual for much of the game but had his moment of glory in the final when he scored the second goal in a 2-0 win over Man United.
Arsenal 2 Barcelona 1 - 1st knockout round, 1st leg, February 2011
Messi provided the assist for David Villa to put Barcelona ahead before half-time at the Emirates. He then had a goal ruled out for offside and wasted two guilt-edged opportunities before late goals from Robin van Persie and Andrey Arshavin stunned the visitors.
