With the win, unbeaten Barcelona has 46 points in 18 games, while Real coach Manuel Pellegrini was left at 41 after losing his visit Athletic Bilbao.
Barcelona took revenge Sevilla last week that kept him out of the Copa del Rey Odds.
Julien Escude against their fence, in the 49th minute, Peter at 70 'and Messi at 85' and 91 ', scored for the defending champion.
With his goals, Messi became the top scorer with 14 goals, two more than David Villa, Valencia striker, also reached 100 points with Messi .
In an encounter that was played earlier, the Madrid blew a good opportunity to remain as interim leader of the League after losing 1-0 against Athletic.
The inspired Bilbao goalkeeper, Gorka Iraizoz, refused repeatedly to the goal box Pellegrini, who scored his third defeat.
The Basque left early to intimidate his rival, and midfielder Carlos Gurpegi and striker Tobias Mikaelsson had opened the account just the first minute of the match.
A disadvantage was surprised Madrid two minutes later when Lassana Diarra could not control Fran Yeste, who crossed for Fernando Llorente scored the 1-0 unmarked in the eyes of the goalkeeper Iker Casillas.
Karim Benzema, Cristiano Ronaldo and Kaka had numerous options to beat Iraizoz, but the draw did not come.
Gurpegi was ejected in the fifth minute of added time for a second yellow card.
In another match, Bridge and Uruguayan Walter Pandiani before 10 minutes sealed victory Osasuna 2-0 at home to Espanyol.
Juanfran midfielder opened the scoring in the 7 minutes, after a confusing play in the area.
Pandiani, who had not scored in Pamplona this season, hit a header two minutes later, before the Osasuna midfielder, Rupert, was sent off for a second yellow card near the end of the first part.