The result nevertheless meant Barcelona became the first side to secure qualification for the knockout.
Messi had traveled with the team to Milan but Barcelona coach Ernesto Valverde opted not to risk the star forward, who hasn't played since fracturing his arm last month. The visitors still nearly managed to win the match when substitute Malcom netted with seven minutes remaining, moments after coming off the bench. But Inter has made a habit of scoring late goals and did so again as Mauro Icardi leveled in the 87th.
Barcelona could have won Group B with a victory at San Siro but a combination of wayward finishing and fine saves by Inter goalkeeper Samir Handanovic means it will have to wait until the final two group matches.
"We had a great game," Valverde said. "We played very well. We didn't win but we qualified. So I leave Milan happy."
Barcelona remained top of the group, three points ahead of Inter and six ahead of Tottenham which beat PSV Eindhoven 2-1.
"It's a good point," Icardi said. "The message from this match is that we want to qualify from the group, we wanted to take points from this match knowing that now we have two difficult matches."
Inter plays Tottenham next. It managed a late come-from-behind victory at home in its Champions League opener, with Icardi leveling five minutes from time and Matias Vecino netting a stoppage-time winner.
"Let's hope the same thing happens that happened at San Siro," Icardi added with a laugh.
Messi injured his arm in a Spanish league match against Sevilla on Oct. 20 and missed the 2-0 victory over Inter in the last round, but had been training with the team in recent days.
However, Messi wasn't even on the bench at San Siro.
"It was a decision shared by the team," Valverde said. "We had to take care of the footballer especially in a match like this. It was a top match and very intense, with lots of tackles. You never know how someone can fall and we didn't want take risks."
Luis Suarez has made up for Messi's goals domestically — with five in his past two matches — but has yet to score this season in the Champions League.
The Uruguay forward went close on a number of occasions, and almost gave Barcelona an early lead with an audacious flick that flew narrowly over the bar.
Suarez had two chances in quick succession in the first half but Milan Skriniar cleared from almost on the goalline and the striker's effort from the resulting corner flashed across the area.
Barcelona dominated and had 65 percent of the possession, with 27 shots to Inter's 10.
However, Handanovic was equal to everything the Catalan club threw at him until Valverde brought Malcom on with nine minutes remaining.
And just two minutes later, Malcom had his first goal for the club, curling a shot between two Inter players and into the back of the net. It was Malcom's first goal for the club and the Brazilian was in tears as he was embraced by his teammates.
But Inter substitute Lautaro Martinez also had an immediate impact as his cross was deflected into the path of Icardi, who fired in his third goal in four matches in the competition. It was his seventh goal in his past six Inter matches.
"I think the goal was deserved because of how the team reacted after Barcelona's goal," Inter coach Luciano Spalletti said. "Icardi is the example — after he equalized he took the ball and ran back with it to the center circle. That says a lot, we wanted to win and still thought we could do it."