Pope Francis heads to Mongolia on Thursday, a predominantly Buddhist country with just 1,450 Catholics, which the Vatican hopes can act as a facilitator to improve difficult relations with China.
The chartered ITA Airways plane carrying the pope and his entourage was due to leave Rome at 6.30 p.m. (1630 GMT) for the 9 hour, 30 minute flight to Ulaanbaatar.
It was due to fly over China for about an hour before crossing into Mongolia. Francis will send a message from the plane to Chinese President Xi Jinping, as he does with the heads of state of every country he flies over.
While the messages are pro-forma, usually invoking God's blessings on a country and its people, the one to Xi could be significant because of the Vatican's difficult relations with Beijing.
Mongolia was part of China until 1921 and has close political and economic ties with Beijing. Diplomats say it could be used as an intermediary with China.
It was not clear if any Catholics from mainland China would cross the border to see the pope.
Visiting places where Catholics are a minority is part of Francis' policy of drawing attention to people and problems in what he has called the peripheries of society and of the world. He has not visited most of the capitals of Western Europe.
The first event for Francis, 86 and in need of a wheelchair, is on Saturday, when he addresses government leaders and the diplomatic corps.
"The pope's visit shows the world that contemporary Mongolia is continuing to accept the freedom of religion and coexistence, peacefully, of religion in Mongolia," its ambassador to the Vatican Gerelmaa Davaasuren, who is based in Geneva, told Reuters in Ulaanbaatar.
Francis is due to attend an inter-religious meeting on Sunday.
One of the topics he is expected to address during the trip is protection of the environment.
Mongolia is one of the countries most affected by climate change, with average temperatures rising by more than 2 degrees Celsius since 1940.
With rainfall in long-term decline, around three-quarters of Mongolia's land is blighted by desertification and drought, and more than 200 small lakes have dried up since 1980.
Ecological problems have been aggravated by overgrazing, with around 80 million animals now trying to survive on land that can sustain only half that number, according to government figures.
The exploitation of mineral resources, seen as one of the only ways to grow the economy, has also put pressure on scarce water supplies.
Ulaanbaatar is one of the most polluted cities in the world, largely as a result of coal burning.
Francis announced on Wednesday that he will release a new document on the protection of nature to update his landmark 2015 encyclical.
Mongolia has seen a revival of Tibetan Buddhism since the collapse of the Soviet-backed Communist government in 1990 and the Dalai Lama is regarded as its main spiritual leader.
However, China has repeatedly put pressure on Mongolia not to allow the 88-year-old exiled Tibetan leader to visit, branding him a dangerous separatist.