Some 5,000 people joined the rally, called to promote the "battle against Jerusalem's Judaization." The event coincided with the anniversary of the United Nations' partition plan in 1947, which called for the establishment of a Jewish state.
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However, most worshippers who prayed at the mosque Friday quickly left it before the Muslim Brotherhood's rally got underway. A group spokesman urged attendants to remain for the protest, asking them not to create a bad impression for the media by leaving.
Propaganda material ahead of Egypt's parliamentary elections was also handed out at the site.
Spiritual leader Dr. Ahmed al-Tayeb charged in his speech that to this day Jews everywhere in the world are seeking to prevent Islamic and Egyptian unity.
"In order to build Egypt, we must be one. Politics is insufficient. Faith in Allah is the basis for everything," he said. "The al-Aqsa Mosque is currently under an offensive by the Jews…we shall not allow the Zionists to Judaize al-Quds (Jerusalem.) We are telling Israel and Europe that we shall not allow even one stone to be moved there."
Throughout the event, Muslim Brotherhood activists chanted: "Tel Aviv, Tel Aviv, judgment day has come."
Speaking to Ynet outside the mosque following the prayer, elementary school teacher Ala al-Din said that "all Egyptian Muslims are willing to embark on Jihad for the sake of Palestine."
"Why is the US losing in Afghanistan? Because the other side is willing and wants to die. We have a different mentality than that of the Americans and Jews," he said.
Eldad Beck is reporting from Cairo on behalf of Ynet and Yedioth Ahronoth
Roee Nahmias contributed to the story