Chapel Hill police say someone left a makeshift bomb -- a 20-pound propane tank -- in the drop box of the shelter, causing a fire and small blast.
A handful of animals died; damage to the building is estimated at $10,000.
Several people were working in the shelter at the time. One staff member heard the bomb go off, saw flames and called 911.
"There was an explosion in the night deposit box and it killed all of the animals in the night deposit room, which is the wildlife room. They were able to remove one boa constrictor that we had in there," says shelter director Pat Sanford.
Some employees had just left the wildlife area where a ferret, a rabbit and two baby squirrels were killed.
The dogs, cats and other domestic animals were unharmed. Sanford says quick action by employees helped save the animals.
The shelter had not received any threats. Fire officials are continuing the investigation. Anyone with information is asked to call919-968-2781.