The presence of the rat version of hepatitis E in a human is of "major public health significance", researchers say.
A Hong Kong man developed the disease, according to new research from one of the city's leading universities.
There had been no evidence until now that the disease could go from rats to humans, and the finding is of "major public health significance", the University of Hong Kong said.
"This study conclusively proves for the first time in the world that rat HEV can infect humans to cause clinical infection," it said.
The disease was found in a 56-year-old man who repeatedly produced abnormal liver function tests following his liver transplant.
Researchers believe he may have contracted the illness through food infected by rat droppings, according a report in the South China Morning Post.
He is now recovering after being treated for the virus, the newspaper said.
Rat hepatitis E virus is very distantly related to human hepatitis E virus variants, the researchers say.
The human version of hepatitis E is a liver disease that affects 20 million people globally each year, according to the World Health Organisation.
Symptoms include fever, vomiting and jaundice, and in rare cases liver failure.
Rodent problems in Hong Kong have escalated in recent months because of a sustained spell of hot and humid weather.