"Mr Mehlis: We are not murderers," read one banner, referring to the German prosecutor who wrote the report that implicated top Syrian security officials in the February killing.
Organised to show support for the beleaguered government of President Bashar al-Assad, Monday's demonstration in central Damascus comes a day before the UN Security Council is due to debate the report.
The US and Britain are calling for the council to take a firm stand on Syria.
"With our soul and our blood, we redeem you, Bashar," the crowd chanted in Sabe Bahrat Square. The people held up large posters of al-Assad as well as his father, the late president Hafiz al-Assad.
The protesters shouted slogans against the US, and unfurled banners with messages such as: "Get away from Syria" and "Syria will never be another Iraq."
In an attempt to draw pan-Arab solidarity, one banner read: "Wake up Arabs, your turn will come soon."
To ensure a big turnout, the government granted students a holiday and encouraged civil servants to attend. Officials from the ruling Baath Party took part in the demonstration, which was organised by state-controlled labour unions.
Police blocked roads to traffic to make way for the protest.
US Secretary of State Condoleezza Rice and British Foreign Secretary Jack Straw have called on the world to take a strong position on the UN report, which alleged that the Syrian and Lebanese intelligence services were complicit in the bombing that killed al-Hariri and 22 other people in Beirut on 14 February.
Syria has dismissed the unproven allegation.
The report also said Syria's government cooperated with UN investigators only "to a limited extent" - a charge that Syria rejected.
"The report is designed to accept different interpretations and that would give any party the chance to create accusations against Syrian and eventually use them against the country"
Nizar Mayhub, spokesman, Syrian Ministry of Information
Nizar Mayhub, spokesman for the Syrian Ministry of Information, told Aljazeera.net the report opened the door for putting pressure on Syria.
"The report is designed to accept different interpretations and that would give any party the chance to create accusations against Syrian and eventually use them against the country.
"Although we have great reservations ... we will continue to cooperate because we have nothing to be afraid of," he said.
"The report indicated that people of a high level of this Syrian regime were implicated," Straw told the BBC on Sunday. "We also have evidence ... of false testimony being given by senior people in the regime. This is very serious."
Straw said earlier that UN Security Council members would consider sanctions against Syria, but it is not clear whether the US and Britain would receive the support of members such as Russia, an old ally of Syria.
For more than a year, the US has been putting pressure on Syria, accusing it of interfering in Lebanon, allowing fighters to cross into Iraq and supporting Palestinian resistance groups.
Syria denies these charges.