Speaking to ITV News, Mr O'Leary said his airline - and most rivals - were arguing that people who are double vaccinated should not have any restrictions.
"That’s what most European countries are applying and the EU… recognised that people who are double vaccinated will not have to isolate or comply with any travel restrictions and Mrs Merkel should do likewise," he said.
It comes after the German Chancellor told the Bundestag on Wednesday that she would like other countries to follow her lead in placing quarantine requirements on British visitors.
She said: "In our country, if you come from Great Britain, you have to go into quarantine and that's not the case in every European country, and that's what I would like to see."
Mr O'Leary said Ms Merkel was "not taking account of the medical situation".
He added: "I would love Mrs Merkel to explain why people who are double vaccinated need to observe any travel restrictions when they're entirely safe and not likely to spread Covid."
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