The new 2,000 pound note went into circulation in several regions including the capital Damascus on Sunday, according to Central Bank governor Duraid Dergham.
"Given the worn nature of the bills currently in circulation, the Central Bank saw that it was the appropriate time to release the 2,000 Syrian pound note," Dergham said, quoted by Syrian state news agency SANA.
The bill features a portrait of Assad on one side and the inside of Syria's parliament on the other.
The value of the Syrian pound has plummeted over the course of the country's war, depreciating by around 90 percent against the US dollar since the conflict erupted in March 2011.
The 2,000 pound note is currently worth approximately $US4.
The largest bill in circulation had been the 1,000 Syrian pound note, which featured Syria's former president and Bashar's late father, Hafez al-Assad.
Reactions to the bill have ranged from expressions of support to concerns that it could spark further inflation.
But Dergham sought to reassure the public.
"There is no need to panic over this matter," he told reporters gathered in Damascus.
