Defunct Tehrik-e-Taliban Pakistan (TTP) has claimed responsibility of the blast.
The explosion took place close to a police building that is not far from the heavily fortified US consulate in Karachi. The Chief Minister House, offices of the security agencies, five star hotels and embassies are also situated in the red zone.
Officials said the CID police building which was demolished completely was apparently target of attackers.
Officials say it might be a car bomb blast that created a wide pit in the ground. Firing was also reported for 10 to 15 minutes before the blast hit the building.
At least 28 people, most of them policemen, are said to be killed in the incident. The death toll may rise.
TV footages showed bloodied victims leaving the scene and security officers searching through the debris of a building. Huge smoke covered the area.
Ambulances and rescue teams thronged to the spot and transferred the deadbodies and injured to hospitals where emergency has been declared.
More than 80 injured were ferried to Jinnah and Civil Hospitals.
The explosion shattered window panes of dozens of buildings. Several houses around the blast site were badly damaged and shaken up after very loud bang hit the CID police office.
A heavy contingent of police and law enforcement agencies arrived at the scene and cordoned off the area. Nature of the blast has not so far been established.
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