Specialist police officers were spotted examining a potential casing on the road after a firearms incident on Deansgate.
Police were called to the scene at 3am this morning (Monday) to a 'report of a man making threats with a firearm'.
The man then fled the scene.
No-one was injured in the incident, the force added.
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A cordon from St Mary's Street to Wood Street was in place on Deansgate throughout the morning, with a large police presence at the scene.
Pictures taken earlier showed Tactical Aid Unit officers examining the area within the cordon.
They appeared to be focusing on what looked to be a casing in the road.
They had sniffer dogs at the scene and were pictured searching through some drains.
Detectives were also spotted going into the Club V nightclub on Deansgate, which is believed to have closed down.
They also appeared to be looking for a bullet hole on the wall above the entrance.
It has not yet been confirmed whether the incident happened inside a premises or out on the road.
GMP have not yet confirmed whether any shots were fired.
A shopkeeper, who works near the scene, told the M.E.N that one of his staff members heard a bang this morning.
He said: "A member of staff was here at about 3am and heard a bang.
"He thought it must be a car crash."
Phil Burke, a spokesperson for Manchester pub and club network, said: "We are aware of a serious incident but as this is a live police investigation cannot comment any further."
In an earlier statement, a GMP spokesperson said: "Police were called around 3am today (13 December) to a report of a man making threats with a potential firearm on Deansgate, Manchester.
"The man subsequently fled the scene.
"Thankfully no injuries have been reported and enquiries are ongoing."
The road reopened at about 1pm.
Anyone with information should contact police on 101 or via LiveChat at www.gmp.police.uk quoting incident 256 of 13/12/21.
Details can also be passed via the independent charity Crimestoppers on 0800 555 111.
