A man has been seriously injured after a charter plane crashed in far northern Western Australia.

WA Police said the aircraft, with two people on board, was coming in to land at Derby Airport when it crashed about 3.20pm on Tuesday in the state's Kimberley region. 

The plane came down on Derby Highway, about two kilometres south of the town site, with police, DFES personnel and paramedics still on scene.

The pilot, a man believed to be in his twenties, suffered serious but non-life-threatening injuries while the passenger is believed to be uninjured.

The two men have been taken to Derby Hospital for treatment. The passenger is stable, while the pilot remains in a serious but stable condition.

Main Roads WA has advised motorists around five kilometres south of the Derby Airport Access Road to take care with emergency services on site.

The spokesperson said the matter would likely be referred to federal authorities for further investigation.

An Australian Transport Safety Bureau spokesman said the circumstances surrounding the crash would be investigated.

"The ATSB will investigate the forced landing of a Cessna 310 aircraft on the highway south-east of Derby on Tuesday afternoon following a reported double engine failure," he said.