Messi, La Liga's joint top scorer this season, is level on 27 goals with Real's Portuguese forward Cristiano Ronaldo who is still recovering from a muscle problem, and could edge ahead when they face third-placed Villarreal.
The World Player of the Year pulled out of Argentina's friendly against Costa Rica on Tuesday as a precaution but tests on the adductor muscle in his right leg on Thursday showed there was no muscle damage.
"I have spoken to Messi and his feelings are positive," reserve goalkeeper Jose Manuel Pinto said at a news conference.
"He is feeling good despite the minor problems he is suffering. We all know Messi and his competitive spirit but the most important thing is his health. He is the one who best knows himself and he will know if he is able to play," he added.
The prolific Messi's presence will be crucial against Villarreal as Barca seek to preserve their five-point lead over Real, whom they play at the Bernabeu in just over two weeks.
That game will be the first of at least two, and potentially four, meetings between the great rivals, who clash in the final of the King's Cup on April 20 and could meet home and away in the Champions League semi-finals at the end of April and beginning of May.
With nine matches left, Barca have 78 points, Real have 73 and Villarreal are on 54, level with fourth-placed Valencia but ahead thanks to a superior goal difference. Valencia play at Getafe on Saturday.
Real coach Jose Mourinho may have to make significant adjustments to his team for Saturday's game at home to Sporting Gijon after the club were hit by what is known in Spain as the "FIFA virus".
In-form France striker Karim Benzema and Brazil full-back Marcelo returned from international duty nursing injuries, a further headache for Mourinho ahead of Tuesday's Champions League quarter-final first leg at home to Premier League club Tottenham Hotspur.
Brazil playmaker Kaka is yet to return after hurting the left knee that was operated on after the 2010 World Cup, while central midfielder Xabi Alonso is suspended for the Gijon match due to accumulation of yellow cards.
Benzema's absence would be a severe blow, although his strike partner Gonzalo Higuain has resumed training and may make his return following back surgery at the start of the year.
If Benzema and Higuain are unavailable, the goal-scoring onus will likely fall on striker Emmanuel Adebayor, on loan from Premier League club Manchester City.
"We have nine games to go, we have to win all those games to start dreaming of the title," Adebayor told Real Madrid Television on Thursday.
At the other end of the table, bottom side Hercules can improve their chances of avoiding relegation with a win at fellow promoted club Real Sociedad on Sunday.
Malaga, in 18th, are bidding for a third straight victory when they play at
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