Iain Bushell, deputy chief officer for Scottish Fire and Rescue Service, told the broadcaster that efforts to bring the fire under control are expected to be "prolonged", and firefighters were facing "an extremely challenging and complex incident".
Crews were called to the building in the city centre at around 11.20pm on Friday and were met with "extremely hard conditions", he said.
There have been no reported casualties at a fire at the School of Art in Glasgow, which was due to be reopened next year after a restoration from a previous fire in May 2014.
An SFRS spokeswoman said: "The Scottish Fire and Rescue Service is now in attendance at a fire in the Mackintosh Building of The Glasgow School of Art".
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More than 120 firefighters tackled a blaze at the School of Art as it underwent a £35m restoration project.
Nearby buildings have been evacuated as fire crews tackle the blaze, which spread "in the space of a few minutes" when it started just around 23:15 BST.
Glasgow Art School devastated by fire for the second time.
Nicola Sturgeon, First Minister of Scotland, tweeted her relief that people were safe but said her heart was also breaking for Glasgow's "beloved" School of Art.
Charles Rennie Mackintosh, one of Scotland's most influential figures, inspired designers, architects and artists around Europe with his distinctive style.
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It seems the results of the fire are once again a crushing blow to Glasgow School of Art, who've worked hard to fix and recover from the 2014 blaze.
It was regarded as his masterpiece, and officials had spared no expense in the restoration that began after the 2014 fire.
The fire in 2014 destroyed the building's library, which was recognised as being one of the finest examples of art nouveau in the world.
The UK government "stands ready to help, financially or otherwise", he added.
Hundreds of people in Scotland and beyond took to social media to express their shock at news footage of the burning building, which some said was as symbolic for Glaswegians as Big Ben was for Londoners.
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