The Damascus International Fair was once the leading event on Syria's economic calendar but had not been held since shortly after the outbreak of the country's war in March 2011.
The Syrian Observatory for Human Rights, a Britain-based monitor of the war, said five people were killed and around a dozen more injured in the rocket fire near the entrance to the fair.
A source at a hospital in Jaramana, an area southwest of the capital, told AFP he had seen dead and injured evacuated from the scene.
There was no confirmation of the toll from officials, and no mention of the incident on Syria's state news agency SANA.
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Syrian state television briefly carried a breaking news alert reporting the rocket fire and saying it had caused injuries, citing its reporters on the scene.
But the alert was removed shortly afterwards, and a reporter broadcasting live from the fair interviewed several officials who made no mention of the rocket fire or casualties.
"We were preparing to receive visitors when I heard an explosion... Then I saw smoke to the side of the of the entrance to the exhibition hall," 39-year-old Iyad al-Jabiri, a Syrian working at a textile stand at the fair, told AFP.
It was touted as a sign that work towards rebuilding Syria and revitalising its ravaged economy was getting underway, despite the violence that continues in parts of the country.
Its general director, Fares al-Kartally, said the decision to hold it this year was a result of "the return of calm and stability in most regions" of Syria.
"We want this fair to signal the start of (the country's) reconstruction," Kartally told AFP earlier this week.
While Damascus has been insulated from much of the worst violence of the country's war, several key rebel enclaves remain in the Eastern Ghouta region outside the city.
In recent weeks, much of the area has been quieter after the implementation in July of a "de-escalation zone" covering parts of Eastern Ghouta.
The trade fair dates back to 1954 but was last held in the summer of 2011, months after the eruption of protests against President Bashar al-Assad's government.
Since then, the country has spiralled into a bloody civil war that has killed over 330,000 people, displaced millions and devastated the economy.
The fair is hosting firms from 23 countries that have maintained diplomatic relations with Damascus throughout the conflict.
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