Police arrested dozens of protest leaders and clashed with hundreds of lawyers and other activists as the protesters attempted to leave Karachi.
The marchers, a coalition of lawyers, opposition party activists and others, are protesting President Asif Ali Zardari's government at a time of increased international pressure on the country, including calls from the United States to focus on threats from Islamist militants within its borders and in neighboring Afghanistan.
U.S. envoy to the region Richard Holbrooke met with opposition party leader Nawaz Sharif in a bid "to get things resolved," Sharif spokesman Sadiqul Farooq told the Associated Press.
The protesters have organized what leaders call a "long march," beginning Thursday with vehicle convoys leaving cities across the Pakistan. They plan to converge at the parliament building in the capital of Islamabad Monday to begin a sit-in.
They are demanding that Zardari, who was elected last year after former military leader Pervez Musharraf was forced to resign, fulfill his campaign promise to reinstate judges fired by Musharraf.
Despite the campaign pledge, Zardari has so far refused to reinstate former chief justice Iftikhar Mohammed Chaudhry. Many analysts speculate that Zardari is afraid Chaudhry will reopen corruption cases against him.
Some lawyers and other activists who had hoped that Zardari would reinstate an independent judiciary now compare him to Musharraf instead.
"Both are brothers," said Mohammad Saleem, a refrigerator repairman in Rawalpindi, where police stopped a lawyer's protest Wednesday, according to the Chicago Tribune. "The elder one is gone, but the younger one is here."
Activist lawyers have been joined by members of the opposition party led by former Prime Minister Nawaz Sharif, who was ousted by Musharraf in 1999. Last month the Supreme Court banned Sharif and his brother from holding elected office, and disbanded the Punjab province's government, which was led by Sharif's brother.
Government officials have sent mixed messages about whether the long march protest will be allowed to go on, saying that peaceful demonstrations would be allowed while continuing to make arrests.
"We'll not stop them, but if someone tries to take the law in his hand I must say in the house that he won't be allowed," Interior Ministry chief Rehman Malik told the National Assembly, according to media reports.
On Thursday, some protesters were allowed to leave Karachi. However, police stopped the convoy at a toll gate at the outskirts of the city, where many leaders were arrested.
Police said 150 people were arrested.
One of them spoke with Reuters in a phone interview from the back of a police van. "This movement is unstoppable. We'll fill the prisons," said Munir Malik, former president of the Supreme Court Bar Association.
Another group of several hundred protesters were allowed to leave the southwestern city of Quetta and had not been stopped by nightfall, according to the AP.