Brussels police said that around 45,000 people attended the rally, which comes just two weeks ahead of regional elections in Catalonia.
A sea of around 45,000 supporters of Catalan independence demonstrated in Brussels on Thursday to back deposed president Carles Puigdemont and urge the EU to stop siding with Spain over the region's independence drive.
Demonstrators chanted "Wake up Europe!" and waved Catalonia's red, yellow and blue separatist flag as they marched past the European Union headquarters in the Belgian capital.
"Have you ever seen a demonstration like this anywhere to support criminals? No!," Puigdemont said in a speech to the crowd, referring to Spanish criminal charges against him, as cries of "president, president" rang out.
Puigdemont and four former ministers fled to Brussels in November, saying they wanted to take their cause to the European level after Spain charged them with sedition and rebellion over Catalonia's independence referendum in October.
The 28-nation EU has so far strongly backed the Spanish government of Prime Minister Mariano Rajoy over the biggest political crisis to hit the country for decades, saying the Catalan issue is an internal matter for Madrid.
On Monday, Spain dropped a European arrest warrant for the five, but Puigdemont said he would stay put for now as they still face arrest in Spain if they return for regional polls in Catalonia that Madrid has called for December 21.
Belgian police said on Twitter that there were an estimated 45,000 protesters, more than double the 20,000 that organisers said they originally expected.
Police monitored the route and a water cannon stood guard outside the European Commission headquarters, but the rally passed peacefully, according to witnesses.
Many of the protesters arrived in a stream of coaches and camper vans after making the 1,300-kilometre (800-mile) journey from Catalonia overnight.
Children and families were among those who filled the streets of Brussels in high spirits despite the cold and rain.
The 2.5 kilometre march took them past the headquarters of the European Commission, whose chief Jean-Claude Juncker was the subject of one placard held by a demonstrator, reading: "Democracy? We defend it when it suits us."
The march ended in a square between the imposing buildings housing the European Council and European Parliament, where Puigdemont addressed them.
The axed leader, wearing a scarf in the bright yellow colour that is the symbol of the independence movement, said that the EU "does not respect the fundamental values of our beloved Europe".
"We want a Europe of free citizens," he added.
The question for now is whether Spain will allow Puigdemont and his cadres back into Spain if they win the upcoming elections.