Is there reason to believe Messi thinks he might not be as successful in the Premiership as he is in La Liga? Messi's strengths are numerous - pace, acceleration, an unbelievable sense of balance, and a technical ability on the ball perhaps unmatched at this point of time. All of these combine to make him an amazing footballer, any way one looks at him. These abilities will definitely allow him to succeed wherever he plays, and yet he looks out of sorts for the Argentine national team. The reason for that is perhaps the way his overall game has been moulded at Barcelona and in La Liga. With a supremely intelligent attacking midfield arrayed behind him, Messi gets the freedom to express himself as only he can, with sublime movement, superb link-up play, and tremendous shooting ability. He does not have the same setup with Argentina, and he suffers because of it.
But perhaps a bigger chink in his armour is the way the game is played in La Liga, where football is almost no longer a contact sport, as fouls are awarded for almost any contact. Thus, opposition players either jostle with Messi for the ball, in which case it's fruitless because the ball literally sticks to his feet, or they just stand off him, which is why he scores some very remarkable goals from range. No doubt, this has helped build up his ability to take long-range shots, but it has also made him vulnerable to a more physical form of football.
Inter Milan were not afraid to tackle Messi. Zanetti and Cambiasso were constantly on his heels, and the latter won the ball off him several times. In fact, the counter-attack for Inter's second goal at the San Siro started by Cambiasso taking the ball off Messi with a classic tackle which felled the Barcelona star. In Spain this would've been a definite foul, where in other leagues, this was legitimate. Messi's calls for a foul went unheard, and Inter scored.
The Premier League is a much more physically imposing league (for example, Zoran Tosic, a Serbian international, was not deemed strong enough for the Premier League when he joined United last year) with a lot more tackling involved. Messi, being Messi, would get a lot of attention from opposition defenders, the same way Ronaldo used to, with players barging into him, tackling from behind, pushing hard while jostling for the ball, and the like.
He is certainly no diver; in fact, his is one of the cleanest in the games. But would he be able to withstand this constant physical barrage from defenders? His closest competitor, Ronaldo, firstly beefed himself up to withstand the constant tackling, and then began diving to discourage foul play. Also, as his strength and other physical attributes improved, players began to stand off him as he made runs because he could now return the favor in the same coin. Messi would not be able to do so in the Premier League. Messi's game is very reliant on him being light on his feet and his inherently low centre of gravity. This allows him to make rapid change of direction, a major weapon in his armoury. Beefing up would rob him of this capability, which would rapidly reduce his effectiveness.
Would Messi be able to adapt his game to this (Premeier League) style? Ronaldo developed his game on these lines and has continued to play in La Liga with continued success. It was easy for him to excel in the Premier League. The question stands: Can Messi, if he plays in the Premier League, remain good enough to retain his "best-player-on-the-planet" tag? The possibility of such a talent failing is best not considered. Hopefully, one day he will join English Premier League and become better than Ronaldo.