Indonesian authorities say they have regained control after protesters set fire to a local parliament building in the eastern province of West Papua.
Businesses, trees and vehicles were also damaged in the unrest in the capital Manokwari.
Violence broke out on Monday over claims of racism toward Papuan students elsewhere in Indonesia.
Comprising what are now Papua and West Papua provinces, Papua became part of Indonesia controversially in the 1960s.
The former Dutch colony declared itself independent in 1961 but its larger western neighbour later took control.
A referendum on its independence was then held in 1969. Though it was overseen by the United Nations, many consider the vote flawed because only slightly more than 1,000 people were allowed to take part.
A separatist movement continues to this day and Indonesian authorities have faced allegations of human rights abuses in the region.
The latest anger stems from an incident involving Papuan students in Surabaya, East Java - Indonesia's second biggest city - over the weekend.
Forty-three students were taken into police custody over reports an Indonesian flag was found damaged outside their building amid national independence day celebrations.
A local police spokesman told ABC Australia they stormed the building over fears a crowd outside were "close to attacking" the group. Activists claim police used tear gas during the raid.
Papua province Governor Lukas Enembe said people were angry because of the "extremely racist words" used by locals and officials during the incident. The governor of East Java has apologised in a televised statement, Reuters reports.
National Police spokesman General Dedi Prasetyo said the students were released after being questioned.
A reporter from the AFP news agency estimated that several thousand people took to the streets of Manokwari on Monday.
Police officials told Reuters that another 500 were estimated in Jayapura - the region's biggest city, and the capital of Papua province.
Images from Manokwari showed plumes of smoke as protesters gathered in the streets.
Some protesters were seen displaying the Morning Star flag - used by pro-independence groups - and shouting separatist slogans.
"Most of them were provoked by content circulating in social media about the racial abuse of Papuan students in Surabaya," Gen Prasetyo said on Monday.
News of the unrest spread across social media - with almost 100,000 mentions of Papua on Twitter by 17:00 local time (10:00 GMT) in Indonesia.
The Indonesian government considers Papua an integral part of the nation. The region is incredibly resource rich and is home to the world's biggest gold mine - one of Indonesia's largest taxpayers.