Police said that a "powerful blast" had occurred at the Tingvallagymnasiet in Karlstad in central Sweden at around 3pm.
The alarm was first raised after people in the area said they had heard a bang and then saw a large column of smoke coming from the roof of the high school. Witnesses also reported they had seen two men running from the area.
"There was a massive explosion, the windows and parts of the walls began to shake," the school's headmistress Christine Holmberg told Swedish tabloid Aftonbladet.
Emergency services were sent to the scene and there were no reports of injuries.
"We are trying to put together to get a picture of what has happened," Stefan Wickberg, a spokesperson for the regional's police force, told The Local.
He said that the force of the explosion had caused car alarms to go off in the area and that police officers were checking out varied accounts of exactly what happened.
Emergency services at the scene. Photo: Tommy Pedersen/TT
By 4.40pm the region's fire and rescue service reported that its staff as well as police had left the scene.
"We can't find an explanation. Our theory is that someone has made something explode that hasn't left any traces. Nobody has been injured," the service wrote on its Facebook page.
The school is the oldest in Karlstad, dating back to the 1800s, according to its website. Its pupils are aged 15 to 19.
All buildings on the site have been evacuated.