Several people were still missing on Tuesday.

Emergency services took three hours to extinguish the fire at the Chempark site, home to chemicals companies Bayer and Lanxess, that flared up after the blast at 9.40am, park operator Currenta said.

"My thoughts are with the injured and with loved ones," said Chempark chief Lars Friedrich.

"We are still searching for the missing people but hopes of finding them alive are fading," he added.

Police said five of the 31 injured people were affected seriously enough to need intensive care.

"This is a tragic moment for the city of Leverkusen," said Uwe Richrath, mayor of the city.

The area and surrounding roads were sealed off for much of the day.

Police told residents living nearby to stay indoors and shut doors and windows in case there were toxic fumes.

Currenta said locals should also turn off air conditioning systems while it measured the air around the site for possible toxic gases.

Chempark's Friedrich said it was not clear what had caused the explosion, which led to a fire starting in a tank containing solvents.

"Solvents were burned during the incident and we do not know precisely what substances were released," Friedrich added.

"We are examining this with authorities, taking samples."

Sirens and emergency alerts on the German civil protection agency's mobile phone app warned citizens of "extreme danger".

Leverkusen is less than 50km from a region hit last week by catastrophic floods that killed at least 180 people.

More than 30 companies operate at the Chempark site in Leverkusen including Covestro, Bayer, Lanxess and Arlanxeo, according to its website.

Bayer and Lanxess in 2019 sold Chempark operator Currenta to Macquarie Infrastructure and Real Assets for an enterprise value of 3.5 billion euros ($A5.6 billion).

Australian Associated Press