About 10 fire crews from throughout the region, including three fire appliances from Invercargill, attended the incident at the large factory after being alerted at 4.36pm.
The Korean-owned plant makes specialised wood products, including wood panels, for the New Zealand market and for export.
Southland fire chief Bruce Stubbs said the cause of the fire was not known. However, it was believed to be linked to a separate callout in the plant's press hall at 12.25pm today.
''It appears that there may have been some hotspots in another part that we weren't aware of,'' Mr Stubbs said.
Thermal cameras were being used to ensure all the hotspots from the second fire had been put out, he said.
Company officials later said no-one had been hurt, safety systems had worked well, and there had been a precautionary evacuation.
There had been only minor damage in the area of the press hall, and production would continue. A reporter at the scene said two logging trucks, and other vehicles could be seen parked outside the usually busy plant at 5pm.
A Fire Service spokesman said appliances from Gore, Mataura, Edendale, Wyndham and Invercargill had been called to the MDF factory after a report of an explosion and ''multiple seats of fire'' at the MDF factory.
Fire Service Southern Communications shift manager Andrew Norris said firefighters wearing breathing apparatus used fire hoses at both fire call-outs.
Firefighters had poured water on parts of a ventilation system to cool it down, and pipes used to transport fibre material within part of the plant had been disconnected to be checked, Mr Norris said.
Firefighters remained at the plant for about four hours after the second call-out.
Earlier media reports indicate that in November last year the plant's energy centre went on fire and in April this year an explosion and minor fire also prompted a fire callout.
