Messi says it would be a special moment to score his 500th career goal in Saturday's Clasico at Camp Nou.
The 28-year-old struck his 50th international goal from the penalty spot in Argentina's 2-0 World Cup qualifying victory over Bolivia on Tuesday.
That strike put Messi on 499 in his senior career and the five-time Ballon d'Or winner has set his sights on hitting his next milestone against fierce rivals Real Madrid.
"It would be a nice moment to reach that figure against Real Madrid. It would be nice to win to stretch our advantage," he said.
Messi has received heavy criticism from fans in Argentina in the past two years, predominantly as a result of Gerardo Martino's side losing the finals of the World Cup and the Copa America.
But the captain was keen to praise supporters for their backing in Cordoba as his side made it three wins in a row in World Cup qualifying.
"I'm happy with the six points, which were our objective in these matches," he added. "The welcome we received was nice. Again the fans gave us a lot of support."
