Office of the Supreme Leader/AP Photo

While President Obama spoke to Israeli students in Jerusalem today, nearly 1,000 miles away Iran's supreme leader issued a fiery threat to the coastal cities of Tel Aviv and Haifa.

"At times the officials of the Zionist regime (Israel) threaten to launch a military invasion," said Ayatollah Ali Khamenei in a televised speech marking the Persian New Year, Nowruz.

"But they themselves know that if they make the slightest mistake the Islamic Republic will annihilate Tel Aviv and Haifa to the ground," he said.

The powerful cleric's strong words come a day after President Obama told Israeli Prime Minister Benjamin Netanyahu that the U.S. would not stand in the way if Israel decided to take unilateral action.

"We have different vulnerabilities… different capabilities… Israel has a right to independently defend itself," Obama said at Wednesday's joint press conference with Netanyahu.

Iran is at the top of the agenda during Obama's Middle East trip, and he reiterated Wednesday America's preference for diplomacy before military action.

"I think there's time to resolve this issue diplomatically," Obama said. "The question is will Iranian leadership seize opportunity."

But Khamenei said he was "not optimistic about [direct U.S.] talks, but [he was] not opposed to it either."

He added that until the stiff international sanctions are relaxed, the nuclear issue will likely remain unresolved. Khamenei admitted that sanctions "have had an effect," and data shows the Iranian rial continues to weaken and revenue from oil and gas exports has plummeted 50 percent in the last two years.

Khamenei told the crowd today that trust has grown increasingly thin between the U.S. and Iran.

"We have repeatedly told you that we are not after nuclear weapons. You say you don't believe us. Why should we believe you?" he asked. "When you are not ready to accept an honest and logical remark, why should we accept your words that have been disproved many times?"

After the last round of nuclear talks ended without a breakthrough, the so-called P5+1 group which includes France, Germany, the U.S., China, Russia and Britain, will return to Almaty, Kazakhstan on April 5-6 to continue negotiations with the Islamic Republic.