Militants on a motorcycle tossed a bomb onto the sprawling campus of the University of Aden, the officials said. It shattered windows at the College of Commerce and Economics, sending terrified students running for safety.
There was no immediate word on casualties or a claim of responsibility.
A university official told the AP that Islamic militants had vowed to attack the school if it did not segregate classes by gender.
The Arab world's poorest country has been embroiled in fighting between Shiite Houthi rebels allied with army units loyal to former President Ali Abdullah Saleh and the internationally recognized government backed by a Saudi-led coalition. Extremists have exploited the subsequent chaos.
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Attempts to ramp up security in the government-controlled city were unsuccessful due to a lack of funds, several government officials said. As a result, the coalition has decided to fund and train nearly 6,000 pro-government fighters to join Aden's overwhelmed police force in the coming days, the officials said.
Also Wednesday, Aden's governor, Gaafar Mohamed Saad, said local security officials associated with Saleh will not be allowed to have a role in running the city. Saleh's forces and the Houthi rebels were expelled from Aden in July.