In an online audio message Sunday, Al-Qaeda chief Ayman al-Zawahiri urged Syrian rebels to fight to establish an Islamic state in Syria.
"Let your fight be in the name of Allah and with the aim of establishing Allah's sharia (law) as the ruling system," he said in his first message posted on the Internet since last November.
"Do all that you can so that your holy war yields a jihadist Islamic state," said Zawahiri, adding that such a state would help to re-establish the Islamic "caliphate" system of rule.
"The enemy has begun to reel and collapse," he said, referring to forces loyal to Assad.
Islamist rebel groups such as the Al-Nusra Front, which has links to Al-Qaeda, have eschewed the main opposition National Coalition, making it clear their goal is the creation of an Islamic state to replace President Bashar al-Assad's regime.
Zawahiri's message will not sit easily with Western powers, who have expressed fears of extremist Islamism playing a growing role in the Syrian conflict and are reluctant to arm the rebels on the ground.
Assad's regime has long dismissed the rebels as "terror" groups backed by Western powers and driven by Al-Qaeda-style ideologies.
According to figures released by the United Nations, more than 70,000 people have been killed in Syria's two-year conflict, which broke out after the army unleashed a brutal crackdown against dissent, turning the uprising into a bloody insurgency.
Zawahiri in his message also warned France over its military involvement against Islamists in Mali, saying it will be defeated, as he alleges, America was defeated in Iraq and Afghanistan, AFP reported.
"I warn France that it will face, God willing, the same faced by America in Iraq and Afghanistan," said the man who took over the leadership of Al-Qaeda after Osama bin Laden was killed by a U.S. commando in May 2011.
"I call upon our Muslim nation in Mali to hold and be patient, and hopefully, effect a new defeat to the global crusade," he added.
France sent troops to Mali in January to block an advance on Bamako from the north by Islamist fighters. It is preparing however to hand over to a UN-mandated African force of 6,300 in the coming weeks.