The Argentine has shrugged off a knee injury picked up during the week to be named in his team's starting XI as he chases Gerd Muller's record of 85 goals in a calendar year
Tito Vilanova makes wholesale changes to the youthful side that drew 0-0 against Benfica, as only two players keep their place in the starting XI.
Victor Valdes returns in goal, while Carlos Puyol and Adriano retain their positions in defence as Gerard Pique and Jordi Alba replace Martin Montoya and Carles Planas for the Catalan giants.
Cesc Fabregas completes a midfield trio with Xavi and Sergio Busquets, while Pedro and Andres Iniesta play either side of Messi, who is just a single goal behind Gerd Muller's record of 85 goals in a calendar year, set back in 1972.
Pepe Mel makes just a single change to his team that beat Deportivo 3-2 last week, as Juan Carlos returns from injury to start in place of Jorge Molina.
On-loan striker Joel Campbell keeps his place upfront for the home side, after scoring in the win over Deportivo.
Betis (4-3-3): Adrian; Chica, Amaya, Dorado, Nacho; Canas, Benat, Salva; Juan Carlos, Campbell, Ruben Castro
Subs: Casto, Angel, Ruben Perez, Pozuelo, Molina, Nosa, Vadillo
Barcelona (4-3-3): Valdes; Adriano, Pique, Puyol, Alba; Xavi, Busquets, Cesc; Pedro, Messi, Iniesta
Subs: Pinto, Alves, Mascherano, Song, Thiago, Alexis, Villa