The exchange of gunfire took place at about 02:30 local time (07:30 GMT) at a concert, but there was no immediate information about a suspect.
Police and local officials said the incident was not terrorism-related.
The mayor of Little Rock, Mark Stodola, said it was the result of a disagreement involving a number of patrons at the Power Ultra Lounge nightclub, which quickly escalated because of "the presence of rivalries and weapons".
"I want to reassure our public that this was not an act of terrorism, but a tragedy... It does not appear to be a planned shooting," Mr Stodola told reporters.
He said that all of the 28 people injured in the incident were expected to survive.
Little Rock police chief Kenton Buckner said the authorities were investigating whether a longstanding rivalry between gangs was to blame.
Special agents from the Bureau of Alcohol, Tobacco, Firearms and Explosives were also assisting local police.
Read more: http://www.bbc.com/news/world-us-canada-40467522