"For me, the national team is over." he said after defeat by Chile in the Copa America final. "I've done all I can. It hurts not to be a champion."
Messi, 29, has won eight La Liga titles and four Champions Leagues with Spanish side Barcelona.
But his only major international honour is Olympic gold at the 2008 Games.
As well as losing two Copa America finals on penalties to Chile, Messi was in the Argentina side beaten
The forward, who was been awarded the was also on the losing side against Brazil in the 2007 Copa America final.
"It's been four finals, I tried," added Messi, who made his debut for Argentina in 2005 and has played 113 times for his country.
"It was the thing I wanted the most, but I couldn't get it, so I think it's over.
"I think this is best for everyone. First of all for me, then for everyone.
"I think there's a lot of people who want this, who obviously are not satisfied, as we are not satisfied reaching a final and not winning it.
"It's very hard, but the decision is taken. Now I will not try more and there will be no going back."
Messi had scored five times at this year's Copa America, including a superb free-kick in the semi-final win over hosts the USA.
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