"We are working on a trade investment framework which will improve the climate for investment, which I know many American firms want to do," Ms Rice said.
"We are co-operating on Libya's membership of the security council of the United Nations," she said, although she pointed out that discussions were in the early stages.
"The relationship (between the US and Libya) has been moving in a good direction for some time but we have a long way to go", she said, adding "we have established a good framework for our relationship."
Ms Rice spent more than two hours in a private meeting with Mr Gaddafi.
She said she had sought to reassure Mr Gaddafi about US plans to establish a major base in Africa - known as Africom - saying its purpose was to "help Africans to help themselves" on issues such as peacekeeping.
She repeated that the US did not have "any permanent enemies".
When asked if she had raised human rights issues with Mr Gaddafi, Ms Rice said she had raised cases "in a respectful manner", and emphasised "that it is important to maintain an open dialogue, including on human rights".
Libyan Foreign Mininster Abdel Rahman Shalgam said that Ms Rice's presence was proof that Libya, the US and the world had changed.
However, the BBC's Rana Jawad in Tripoli says that far from a hard-hitting encounter that brought anything new to the table, Ms Rice's visit to Libya proved only to be a symbolic gesture of diplomacy by the Americans.
Although both sides refrained from calling each other friends, they seemed eager to sustain the momentum of bridging gaps in a relationship that has long been in a state of disarray, she adds.
Ms Rice is the first US Secretary of State to visit Libya since 1953.
She met Mr Gaddafi at the same compound in Tripoli which was hit in US bombing raids ordered by Ronald Reagan in 1986.
Libya was on the US state department list of sponsors of terrorism until 2003, when it abandoned weapons of mass destruction and renounced terrorism.
Earlier this month, Libya agreed to pay compensation to families of the victims of the Lockerbie aircraft bombing, for which it formally accepted responsibility in the same year.
The deal includes compensation for Libyan victims of the United States' retaliatory bombing raid over Libya in 1986.
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