The Argentina international netted a leveller in the reverse match last month to ensure that his side are favourites to progress through, as they look to build on the 1-1 draw claimed in West London.
Messi has scored in each of his last four games for the Catalan giants, netting five in total during that spell, but he does not boast the best of records against Chelsea.
Ahead of the midweek tussle in Catalonia, Sports Mole takes a closer look at how the five-time Ballon d'Or winner has fared against the reigning Premier League champions in previous meetings.
Not until that most recent encounter on February 20 had Messi found the net in a competitive match against Chelsea - a run spanning eight scoreless games since his first outing against them in 2005-06.
As incredible as it is to think, the little maestro has now been terrifying defences for 14 years, and he hit the bar in the first leg of their last-16 tie that season on just his third start in the competition.
Messi made less of an impact in the reverse match, however, being withdrawn 25 minutes in through injury, and he was also unable to make a telling impact in the following season's group-stage ties.
Barcelona lost 1-0 at Stamford Bridge and drew 2-2 at Camp Nou, while two years on there was to be similar frustration for the Catalan giants for large parts of their semi-final showdown.
In a second leg now infamous for the refereeing of Norwegian referee Tom Henning Ovrebo, long-serving midfielder Andres Iniesta found a late away goal to send his side through after latching on to a Messi pass.
That would prove to be one of three occasions the Argentine has played a direct part in a goal involving these two teams, as he also bagged an assist in another famous semi-final meeting between the sides in 2011-12 after hitting the woodwork twice - once from a penalty - and on this occasion his night ended in disappointment as Chelsea went through with a late goal.
Last month's second-half strike in the English capital therefore ended a goalless drought spanning some 730 minutes, and now all eyes will be on Messi to see if he can conjure up yet more magic in what should be another heavyweight battle.