The pro-opposition Syrian Observatory for Human Rights said 15 rebels and at least 16 soldiers were killed.
The British-based Observatory said the checkpoint explosion, near the suburbs of Mleiha and Jaramana, was detonated by a suicide bomber from the al Qaeda-linked Nusra Front.
Nusra supporters on Twitter, however, said the bomber had intended to blow himself up in the car, but instead got out before setting off the explosives inside. They said rebel forces had captured the checkpoint hit by the car bomb and were battling to take a second one nearby.
Syrian state television reported the blast but gave no death toll, saying only that several people had been killed or wounded in a "terrorist bombing".
The Observatory, which has a network of activists across Syria, said Syrian fighter jets retaliated by striking nearby opposition-held areas such as Mleiha.
Video uploaded by activists showed a huge column of smoke billowing up from the scene, and the sound of fighter jets streaking overhead could be heard.
Rebels also fired rockets into Jaramana, a suburb held by the government, according to the Observatory. It said the air force carried out four strikes on adjacent rebel-held districts.
More than 100,000 people have been killed in Syria's 2-1/2-year-old conflict, which began with popular protests against President Bashar al-Assad before degenerating into civil war. The war has pitched most of the country into violence along sectarian and ethnic lines.
In the northern province of Hassaka, a rebel suicide bomber blew himself up at a base belonging to Kurdish militants, killing at least one Kurdish fighter, the Observatory said. Kurdish groups have been fighting for autonomy from both the rebels and the army.
DAMASCUS SUBURB UNDER SIEGE
In Damascus, activists said Syrian forces also tried to storm the suburb of Mouadamiya, which the army has blockaded for months, leading to a rising death toll from hunger and malnutrition.
The army had advanced, but had yet to enter the suburb, said Qusair Zakariya, an activist there.
"Our rebels are fighting hard to repel the regime ... We've been doing our best to try to evacuate civilians from the western front of the town because they're now exposed to shelling and tank fire," he said, speaking by Skype over audible bursts of rocket fire.
Like most rebel enclaves in the suburbs that ring Damascus, Mouadamiya has been under an army-imposed siege for months, causing a particularly acute shortage of food and supplies.
Doctors in the town have reported an increasing number of deaths from malnutrition, especially among children.
The United States condemned the siege on Friday, saying the Assad government had only allowed a limited number of civilians to escape from Mouadamiya and that it must allow food, water and medicine to reach those still inside.
"We also warn the regime ... not to use limited evacuations of civilians as an excuse to attack those residents who remain behind," it said. "The regime's deliberate prevention of the delivery of life-saving humanitarian supplies to thousands of civilians is unconscionable."
The World Health Organization said on Saturday that two suspected cases of polio had been detected in the eastern province of Deir al-Zor, the first appearance of the incurable viral disease in Syria in 14 years.
Western powers have mostly backed opposition forces trying to end four decades of Assad family rule, but have hesitated to supply military aid to the rebels, fearing the rising influence of al Qaeda. Russia and Iran have supported Assad unstintingly.
International efforts to stop the bloodshed in Syria have stuttered for months, but Russia and the United States are now planning to hold peace talks in Geneva next month.
The deeply divided opposition remains reluctant to attend, however, and Assad's government has already said it will not consider any deal that requires the president to step down.
The international envoy for Syria, Lakhdar Brahimi, said during a visit to Cairo on Saturday there would be no preconditions to attending the peace conference.
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