UN human rights chief Zeid Ra?ad Al Hussein said Ashin Wirathu?s comments amounted to ?incitement to hatred?.
The comments related to South Korean envoy Yanghee Lee, who was in Myanmar last week to address the plight of its Muslim minority.
Wirathu spent almost a decade in jail for inciting anti-Muslim violence.
The monk is a leader of the 969 movement, which says Myanmar should remain a Buddhist country and calls for restrictions and boycotts on Muslims.
Mr Zeid called the language ?sexist? and ?insulting?.
?I call on religious and political leaders in Myanmar to unequivocally condemn all forms of incitement to hatred including this abhorrent public personal attack,? Mr Zeid said in a statement.
Since the end of military rule in Myanmar, also known as Burma, in 2011, Buddhist nationalism, largely led by monks including Wirathu, has been energised.
In 2012, scores of people died and thousands were left homeless after violence broke out between Buddhists and Muslims in Rakhine state, mostly from the Rohingya minority. Anti-Muslim violence has flared several times since then.
The UN says the Rohingya are being persecuted, and last week passed a resolution calling on Myanmar to give them citizenship.
Ms Lee, who was on a 10-day trip to the South East Asian country, said the Rohingya faced systematic discrimination.
She criticised draft legislation, proposed by a coalition of nationalist Buddhist monks, that includes curbs on interfaith marriage and religious conversions.
Last Friday, Wirathu spoke at a public rally where he criticised the UN interference and personally attacked Ms Lee, according to local media.
?We have explained about the race protection law, but the bitch criticised the laws without studying them properly,? he said from the stage to the crowd.
?Don?t assume that you are a respectable person because of your position. For us, you are a whore.?
In his statement, Mr Zeid said instead of focussing on people, leaders should address the substance of the concerns raised by the special envoy.
On Wednesday, Myanmar?s government said it was investigating the speech.
The BBC?s Jonah Fisher in Yangon said monks are a powerful political lobby in Myanmar.
With a general election this year the question now is which leaders will speak up and risk Wirathu and the monks turning on them, he adds.