Clashes between Christians and Muslims have left around 1,000 dead in the past two weeks alone.
The crowd waved banners reading "Stop the killings of Muslims" and there were chants of "Jihad" or "Holy War," and "Allah Akbar" - "God is Great."
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The rally, held after morning prayers at Jakarta's National Monument Square, follows a series of smaller protests by Muslims in the capital in recent days.
Around 100,000 people are estimated to have gathered in the park opposite the presidential palace.
The Moluccan islands have been the scene of bitter ethnic clashes between Muslims and Christians .
The Indonesian human rights group Kontras says that more than 4,000 people have died on the island of Halmahera alone since last August.
The conflict that broke out in Ambon in January 1999 has also left more than 2,300 injured and 8,500 buildings, including more than 122 places of worship, either damaged or burned.
Tens of thousands of residents have fled their homes.
Normal situation
One of those at Friday's protest was Amien Rais, speaker of the country's top legislative body.
A leading Muslim and pro-reform figure, he urged: "Return Ambon to its normal situation as soon as possible."
He described the conflict in the Moluccas as a bid to weaken Islam in Indonesia, the world's most populous Muslim nation. Some 90% of the country's 210m people are Muslims.
Another speaker at Friday's rally, Husein Ali Al Habsy, warned: "We give (President Abdurrahman Wahid) one month to stop the killings of Muslims. Otherwise, we are ready to send at least 10,000 people there to defend the Muslims."
Other speakers urged Muslims to register as volunteers to go to the region.
Hamzah Haz, a former senior government minister in President Wahid's Cabinet, called on all government parties to reconsider their support for the Indonesian leader if he fails to resolve the problem.
The crowd also called for the resignation of Indonesia's Vice-President, Megawati Sukarnoputri. Megawati has strong support in the islands and has been asked by President Wahid to try to resolve the conflict.
"Mega - your silence is poison for Ambon," read one banner.
Blockade
Indonesia's navy has imposed a blockade around the Moluccas in an attempt to stop militia members from travelling between islands.
Navy spokesman Commodore Ontowiryo said nine warships and five surveillance aircraft were patrolling the area, and would use force to keep the warring sides apart.
"The water blockade is to prevent ships with unclear missions entering the waters," he said.
Only ships carrying humanitarian aid would be allowed into the area.
"We have already confiscated ammunition, homemade bombs and hundreds of other weapons such as daggers, spears and swords," said another navy spokesman, Colonel Didik Setiyadi.
Public ferries in and out of the major cities of Ambon and Ternate have been suspended due to security fears. The navy has transported about 17,000 refugees fleeing fighting in the islands.