Lawyers have spearheaded opposition to Musharraf since the former army chief tried to dismiss the country's then top judge, Iftikhar Chaudhry, last year. Chaudhry and dozens of other judges were purged after Musharraf declared emergency rule in November.
The protest, due to end in the capital on the weekend, will increase pressure on staunch U.S. ally Musharraf to step down. He has been isolated since his allies were defeated in a February general election and some opponents are demanding he quit and face trial.
"We are out to save the judiciary. We are out to save the country," Mehmood-ul-Hassan, president of the Karachi Bar Association told the rally as lawyers chanted "hang Musharraf" in a street in the centre of Karachi.
Dubbed a "long march" even though the lawyers will travel in a motor convoy from Karachi to Multan, where the march to Islamabad will officially begin, it is the first major protest the new government will have to contend with.
Both sides have vowed to keep the peace, with the government saying the lawyers have the right to protest, but the possibility of violence can not be ruled out.
It could also trigger even deeper splits in the fragile coalition led by the party of assassinated former prime minister Benazir Bhutto, which is seen as dragging its feet on the restoration of Chaudhry and other sacked judges.
Bhutto's widower Asif Ali Zardari, who now leads the party heading the coalition, has called Musharraf a "relic of the past".
Zardari has also said his Pakistan People's Party did not recognise Musharraf as a constitutional president, and has drafted a constitutional package that would reduce him to a figurehead role and lead to the reinstatement of the judges.
Nawaz Sharif, the prime minister Musharraf overthrew and who now leads the second largest party in the National Assembly, wants Musharraf impeached or tried for treason.
Sharif is insisting Chaudhry get his old job back and has already pulled its members out the cabinet after a deadline for their restoration passed. Sharif's party is supporting the rally although he is in London this week.
Analysts said it was not clear how much support the rally would get among ordinary Pakistanis struggling with surging fuel and food inflation, or if discontent over prices would translate into more support for the lawyers.
Chaudhry, who spent nearly four months under house arrest after he was purged, is due to join the rally from Lahore to Islamabad.
A spokesman for the former top judge said it was the duty of all Pakistanis to support the protest.
"We expect that they come out and join us. We have come out to save the country," the spokesman, Attar Minullah, told reporters in Islamabad.
"We don't want any sort of excuses. We want restoration of judges quickly because any delay is a threat to this country and democracy."
The lawyers in Karachi were due to board banner-bedecked buses and cars and drive north for a rally in Multan on Wednesday.
About 1,500 lawyers and activists rallied in Multan on Monday while about 200 protesters demonstrated in the southwestern city of Quetta.
Güncelleme Tarihi: 09 Haziran 2008, 15:39