Pakistan has been a staunch ally of US President George W. Bush since the September 11 terror attacks on New York and Washington.
Rice will fly to the Afghan capital Kabul early on Thursday and then return to Islamabad later the same day for talks with other senior Pakistani figures including her counterpart Khurshid Kasuri.
A Pakistani official speaking on condition of anonymity said on Wednesday that Pakistan was likely to raise with Rice its wish to join an international group fighting the spread of nuclear weapons.
Pakistan's bid to join the 44-member Nuclear Suppliers Group comes despite growing international concern over a black market run by the disgraced father of Pakistan's own atomic programme.
Earlier India and the United States agreed to strengthen co-operation in defence and energy during Rice's flying visit to New Delhi.
The US Secretary of State, who arrived in the Indian capital late on Tuesday, held a flurry of meetings from early morning before departing for Pakistan.
She was upbeat about the peace process between India and Pakistan after talks with Indian Foreign Minister Natwar Singh.
"We very much admire what the (Indian) prime minister and (Pakistani) President Pervez Musharraf have been able to continue, given the change in government here in India," Rice told a joint press conference with Singh.
"It is heartening that dialogue has continued and indeed accelerated and we want to be supportive in any way that we can."
Rice also underlined US co-operation with India to provide relief after the December 26 tsunamis and said it signalled more joint military-to-military exercises.
"Our defence co-operation is strong with military-to-military contacts and joint exercises and the United States looks forward to enhancing that defence co-operation over the next several years," Rice said.
When asked about the possible sale of F-16 fighter jets to India, Rice replied: "The sale of F-16s came up."
She said no agreement would be announced on the issue, adding that the sale of the warplanes would also likely be raised in talks with Islamabad later this week.
Officials here have not said if Rice will make any announcement about Islamabad's request to buy more F-16 fighter jets from the US. India strongly opposes the sale.
The Wall Street Journal reported on Tuesday that on her six-country swing through South Asia Rice is expected to signal US willingness to sell F-16s to both Pakistan and India.
The paper, citing US government sources, said the US could sell Pakistan about two dozen jets while India could buy as many as 125.