"All air defense networks are active to intercept threats," said IDF spokeswoman Effie Defrin.
This is an event different from what we have been through so far and we are expected to have a hard time, he added.
Both Israel and Iran have temporarily closed their airspace. The Flightradar24 flight tracking website found almost no aircraft operating in the sky over Israel and Iran on June 13.
Before more than 100 UAVs were launched by Iran, Iranian Supreme Leader Ayatollah Ali Khamenei pledged to respond to the target of the Israeli attack.
An Iranian armed forces spokesman, Lieutenant General Abolfazl Shekarchi, also vowed to take a strong response to Israel's attack.