NSW Fire and Rescue personnel are attempting to identify a substance leaking from a pipe in Macquarie Street.
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They are also trying to determine the source of the leak.
Emergency services received the call about the substance earlier this afternoon.
It is understood that all businesses in the area, between Church Street and the pedestrian crossing near Riverdale have been evacuated, with the exception of the Amaroo Hotel and Mr Beans Coffee Emporium.
A police spokesperson said there is a possiblity the substance is flamable, however this has not yet been confirmed.
Police attended the scene and have closed Macquarie Street between Church and Talbragar Streets.
They are assisting with traffic management and traffic is being diverted around the area.
Dubbo City Council have also been alerted to the incident and arrived on scene a short time ago.