Nola, one of four northern white rhinos remaining in the world, has died.

San Diego Zoo Safari Park said the rhino had passed away at the age of 41 after a series of illnesses.

"Nola, who lived here since 1989, was under veterinary care for a bacterial infection, as well as age-related health issues," it said in a Facebook post.

"In the last 24 hours, Nola's condition worsened and we made the difficult decision to euthanise her."

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The death leaves three northern white rhinos remaining on the planet.

The San Diego Zoo had lost its other northern white rhino, 44-year-old male Angalifu, to age-related causes in December last year.

The zoo had recently welcomed six southern white rhinos from South Africa as part of a novel conservation initiative to save the northern white rhino from extinction.

The six female southern white rhinos — all aged between 4 and 7 — will hopefully become surrogate mothers to northern white rhino embryos in the ambitious conservation effort.

Researchers at the San Diego Zoo Institute and collaborators "are developing reproductive techniques to develop northern white rhino embryos ... to be implanted in the southern white rhinos, which will serve as surrogate mothers."

"There are many challenges ahead, but researchers are optimistic a northern white rhino calf could be born from these processes within 10 to 15 years," the zoo said.

The zoo's genetics division has been preserving cell samples of wildlife in its so-called Frozen Zoo, including genetic material from 13 northern white rhinos.

If the reproductive technologies are effective, they could be applied to other rhino species, including the Sumatran and Javan rhinos — both also critically endangered.

Over the years, 94 southern white rhinos, 68 greater one-horned rhinos and 14 black rhinos have been born at the zoo.

Rangers feed Fatu (left) and Najin, the two surviving female white rhinos. ( Facebook: Ol Pejeta Conservancy/Erico Hiller )

Nola's death leaves just three living northern white rhinos — two females and a male who all live at the Ol Pejeta Conservancy in Kenya.

Khaled Abol Naga.Sudan is the last northern white rhino male in the world. ( Facebook: Ol Pejeta Conservancy/Teeku Patel )

The male, Sudan, was caught in South Sudan in 1973 and was shipped to the Dvur Kralove Zoo in the Czech Republic.

He was moved back to Kenya in 2009 and is now about 42 years old.

He has sired three offspring, including Nabire, who was born in 1983 and died in the Czech Repbulic this year, and Najin, who was born in 1989 and is still living.

Najin's daughter Fatu, who was born in captivity in 2000, is also still alive and lives with her mother and grandfather at the Ol Pejeta Conservancy.

The three remaining northern white rhinos are guarded 24 hours a day by an armed guard.

Celebrities have also been involved in the plight to save the northern white rhino.

Sudan has received celebrity visits from Bollywood star Nargis Rakhri and Arab actor Khaled Abol Naga.