Victoria Police has arrested two teenagers and seized a machete in relation to the death of a 22-year-old man who drowned in Melbourne's Yarra River last month.

Police allege the man, from Clyde North, died while trying to evade the two teenagers, one of which was allegedly chasing him with a machete, just before 3am on September 30.

His body was located in the Yarra in Melbourne's CBD on October 1.

Police said an 18-year-old Collingwood man and a 16-year-old Melton South boy had been interviewed, arrested and then released pending further inquiries. 

No charges have been laid.

A machete was seized from the Collingwood address, police said.

Police allege the Clyde North man left a licensed venue on Flinders Street shortly after 1am on September 30 before he "had a conversation with a group of males where it is believed an altercation occurred".

"Investigators do not believe they were known to each other," police said.

"[Police allege he] was punched and elbowed to the head, before he ran from the scene. He was chased by two of the men, one of whom brandished a machete.

"Just before 2:50am the Clyde North man jumped into the Yarra River in what will be alleged was an effort to evade them, managing to scramble onto a jetty, before once again falling into the water and subsequently drowning."

Police have urged anyone with further information or CCTV to contact Crime Stoppers on 1800 333 000 or submit a confidential crime report at www.crimestoppersvic.com.au.