The top US diplomat, sent by President Barack Obama on a delicate mission to encourage
nascent reforms in a nation long distrustful of the West, was expected to press the regime on its suspected military ties with North Korea. Clinton kicked off a flurry of diplomatic activity with her first formal meeting with her Myanmar counterpart, Foreign Minister Wunna Maung Lwin, backed by pictures of pagodas at the foreign ministry in the remote capital Naypyidaw.
According to US officials accompanying Clinton, the main focus of her talks with her counterpart would be Myanmar's relationship with North Korea, which is under tight UN and US sanctions for defiantly pursuing its nuclear weapons.
Her aides have, however, played down defectors' accounts of nuclear cooperation between the two authoritarian countries, saying the top US concern relates to missile technology.
Her trip comes amid signs of change in Myanmar, which was ruled by the military for decades until elections last year brought a nominally civilian government to power -- albeit one with close links to the army.
Clinton was also due to hold discussions with President Thein Sein, a former general who heads the new regime and has overseen a series of reformist moves, including dialogue with democracy icon Aung San Suu Kyi.
Later Thursday Clinton will head to Yangon, the commercial hub of the country formerly known as Burma, where she will meet Suu Kyi, who is widely respected in the United States.
The Nobel Peace Prize winner told a conference in Washington via video link on Wednesday she hoped Clinton's visit would spur further reform in Myanmar.
"I hope secretary Clinton's visit will open the way toward a better relationship", Suu Kyi said.
"I've always been in favour of engagement. I would certainly be very happy to see the United States engaging more with Burma."
Aides said Clinton wanted to strike a careful balance -- to press Myanmar on persistent concerns over human rights without emboldening hardliners who could argue that reforms have only led to a public lashing by a high-profile guest.
Thein Sein himself remains a mystery to US policymakers. Clinton met him briefly at last month's East Asia Summit in Bali, but US officials say they do not know how he will react to potential criticism in private.
Speaking on Wednesday in South Korea before flying to Myanmar, Clinton said she wanted to see for herself "what is the intention of the current government with respect to continuing reforms, both political and economic."
"We and many other nations are quite hopeful that these flickers of progress ... will be ignited into a movement for change that will benefit the people of the country."
Clinton has repeatedly said that she does not envision an immediate end to sweeping US sanctions on Myanmar, a step that would require approval from a largely sceptical Congress.
But while officials declined to comment on any announcements they may make in Myanmar, the United States has a number of other tools at its disposal such as stepping up development assistance in one of the world's poorest nations.
The United States could also name a full ambassador to Myanmar. Washington has been represented only by a lower-ranking diplomat as a protest since Myanmar's 1990 elections, which were overwhelmingly won by Suu Kyi's party but annulled by the military junta.
The opposition plans to contest by-elections in a major test for how far the government is ready to accept political reforms. There are 48 seats up for grabs but no date has been set for a vote yet.
Suu Kyi, who spent the best part of two decades in detention at the hands of the generals, had been widely expected to stand in the polls and confirmed this in her remarks by video link.
"I will certainly run for elections when they take place," she said.
Since taking over, Thein Sein has launched dialogue with Suu Kyi and ethnic minorities with which it is fighting some of the world's most long-running wars.
But activists say that anywhere between 500 and more than 1,600 political prisoners remain behind bars and that the situation in ethnic areas remains dire.