Many chanted "freedom for the political prisoners" as they marched along Parallel Avenue, one of the city's main streets, many waving the red and yellow Catalan flag.
"Since they could not decapitate separatism, they are trying to do it through the courts", said Roser Urgelles, a 59-year-old teacher, at the protest. "But we will continue to protest peacefully".
Like thousands of others at the march, she wore a yellow ribbon to show solidarity with the jailed leaders, whom Catalan separatists consider to be "political prisoners".
Spain's justice minister, Rafael Catala, has called the yellow ribbons "insulting", arguing that Spain has no political prisoners but "politicians in prison".
It is estimated that more than 300.000 people participated in the protest.
The demonstration was organised by the National Catalan Assembly and Omnium, a Catalan cultural association.More news: The Weeknd and Bella Hadid rekindle romance at Coacehlla
More news: Silva reflects on 'most special' Man City title in tough year
More news: A Star Wars Story
It is not the moment of trials or arrests, but of building bridges and finding a solution, assured the General Secretary of the UGT of Catalonia, Camil Ros. Spanish and German prosecutors met last week at the headquarters of Eurojust in The Hague.
In 2006, during the time when Zapatero government (PSOE) was in power, the Catalan parliament brought forth demands for increased self-governance in Catalonia through a 2006 Statute of Autonomy of Catalonia, a law passed by the legislature in the autonomous Spanish community, which went on to be approved by Spain's parliament and later ratified in a referendum by Catalan voters.
The movements at the wealthy region has plunged Spain in years.
Catalonia's struggle to find a leader began after it declared independence in October.
Among the politicians facing charges of rebellion is Jordi Sanchez, the latest candidate put forward by Catalan lawmakers to become leader of the region.
However, in those elections, held on December 21, the three pro sovereignty parties revalidated their majority in the Catalan chamber although the legislature has not yet begun after four unsuccessful attempts to invest in a new President. Leaders from both groups were jailed following the referendum. The poll surveyed 1,200 people and had a margin of error of 2.8 percent. If a new leader is not named before the end of May, Catalonia will be forced to call another election.