Champions Real Madrid eased to a 3-0 win over lowly Las Palmas with goals from Gareth Bale and Karim Benzema despite missing six regular starters, including top scorer Cristiano Ronaldo and captain Sergio Ramos.
Franco Vazquez opened the scoring for Sevilla from close range in the 36th minute and Colombia international Luis Muriel doubled the home side's lead by smashing in on the rebound five minutes into the second half.
Messi had began the game on the bench due to continued muscle discomfort which caused him to miss Argentina's friendlies against Italy and Spain and the league's top scorer was called into action in the 58th minute, replacing Ousmane Dembele.
Barca were instantly lifted by the Argentine's arrival and shortly after coming on Luis Suarez rattled the near post but Sevilla continued to pour forward and Vazquez and Muriel each missed clear chances to strike again and put the game to bed.
Barca looked on course for a first league defeat since losing at Malaga last April but Suarez pulled one back with an acrobatic finish in the 88th minute and Messi whipped in the equaliser in the 89th with a venomous left-foot strike.
"Liga games are like this when your rival takes the game to you. They had a lot of chances after making it 2-0 but we showed a lot of pride and we stayed strong mentally," Suarez told reporters.
"That is what Leo is all about as he keeps on showing us again and again. The team just kept on working and didn't give up and it was down to him to score the equaliser."
The goal stretched the Catalans' unbeaten run in the league to 37 games and if they avoid defeat next week at home to Leganes they will equal Real Sociedad's Liga record of 38 games without defeat, which has stood since 1980.
"It was a game in which everything seemed to happen," Barca coach Ernesto Valverde said.
Barca top the standings on 76 points but if second-placed Atletico Madrid beat Deportivo La Coruna on Sunday their advantage at the top will be cut to nine. Real are third on 62.
PHENOMENAL PACE
Bale exhibited his phenomenal pace and power to race on to an exquisite through ball from old Tottenham Hotspur team mate Luka Modric and fire in the opening goal for Real against Las Palmas in the 26th minute.
Madrid's stand-in captain Benzema doubled the advantage from the penalty spot after Lucas Vazquez was fouled before Bale won and converted another spot-kick six minutes into the second half to put Madrid further at ease.
Real defender Nacho Fernandez had to be substituted in the first half with a thigh strain and the Spaniard was seen crying as he sat on the sidelines with the injury likely to rule him out of Tuesday's Champions League quarter-final first leg at Juventus.
Zidane left Ronaldo, Marcelo and Toni Kroos at home for the trip to the Canary Islands and was without Isco and Ramos due to injury and Dani Carvajal through suspension, meaning his squad will be well rested for the trip to Turin for a re-run of last year's Champions League final.
"This was a complicated game for us after the international break and we got an important victory which will serve us well going into Tuesday's game," Real winger Vazquez said.
(Reporting by Richard Martin, editing by Ed Osmond)
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