Police were called to the Moonie Highway in Kumbarilla, around 118km from Toowoomba, around 4.30am after a collision between a car and a fuel tanker, which overturned the tanker.
Two men escaped the wreckage with only minor injuries.
One man was left with a head injury and the other suffered an injury to his eye, Queensland Ambulance confirmed.
The car and truck drivers were taken to Dalby Hospital where they remain in a stable condition.
The crash caused a “significant amount” of fuel to spill onto the road and police declared the incident under the public safety preservation act.
Officials said they are unsure of the type of fuel but diesel was in the mix.
An exclusion zone has been set up across Moonie Highway south to Kumbarilla Lane, north to Gulera Daandine Road and 500m east and west of these areas.
It is expected traffic diversions on the Moonie Highway will remain for several more hours.
Residents have been warned to stay inside, keep windows closed and to keep any respiratory medicine easily available.
Drivers and members of the public have been asked to avoid the area.
