"Iran has a way out if they ever wish, but we will seriously pursue sanctions if they don't," Rice told Yahoo! News and the magazine Politico.
"You have to hope that there are reasonable people in Iran who see this as not the way to run a country."
Tehran's latest response to a demand for the enrichment freeze in exchange for trade and technology incentives "is not a really serious answer," she said in her first comments since six world powers discussed the matter in a Wednesday conference call.
In the interviews, Rice said that the United States does not view Iran as "a permanent enemy," and has "been pretty tough with them already" by backing three sets of United Nations sanctions.
"They should have felt like time is running out quite a long time ago," Rice said.
"When you are having trouble getting banks to come in, getting investment, when export credits are going down from around the world, when you have inflation roaring, time is running out," she said.
On Wednesday, Britain and the United States said the six powers now had "no choice" but to seek new UN sanctions after Iran failed to give a "clear positive response."
The two governments said there was now agreement among the six powers, which also include China, France, Germany and Russia, that a new sanctions resolution should be discussed at the Security Council.
Washington and its allies say Iran's nuclear program could be a cover to develop atomic weapons.
Iran insists it has the right to develop nuclear technology, which it says is aimed at generating electricity for its growing population.
