Damascus on Thursday accused joint UN-Arab League peace envoy Lakhdar Brahimi of "flagrant bias" against it, AFP reports.
The accusations were made a day ahead of talks Brahimi was to hold with top U.S. and Russian officials on Syria's conflict.
The sharp broadside against the veteran Algerian diplomat, who has tried since September to quell the violence in Syria, revealed rising diplomatic tensions over the country's 21 months of violence.
It came in reaction to Brahimi's comments that a three-stage road map President Bashar al-Assad proposed last Sunday to negotiate a "political solution" with approved elements of the opposition was "one-sided".
"Syria is shocked by the statements of Lakhdar Brahimi, who has overstepped his mandate and exhibited a flagrant bias for those parties known to be conspiring against Syria and its people," the Syrian foreign ministry said in a statement broadcast by state television.
Brahimi on Wednesday told the BBC that Assad's plan to keep fighting rebel "terrorists" and ignoring opposition groups tied to them, while offering limited dialogue only to domestic opponents deemed acceptable was "not really different and it is perhaps even more sectarian, more one-sided."
Brahimi said Assad needed to acknowledge "there is a problem, a very, very serious problems between Syrians, and that Syrians have got to talk to one another to solve it."
Even more stingingly to Assad, who took over from his long-reigning father in 2000, the envoy said, "In Syria in particular, what people are saying is that one family ruling for 40 years is a little bit too long."
Syrian state media led the first attack on Brahimi, AFP reported, with the pro-government Al-Watan newspaper calling him a "pawn" of the West, before the foreign ministry took up the charge.
The scathing exchange appeared to undercut further any prospect of international diplomacy working on Assad to calm what has become a civil war in Syria, with more than 60,000 deaths according to the UN.
On Friday, Brahimi was to meet in Geneva with Russian Deputy Foreign Minister Mikhail Bogdanov and U.S. Deputy Secretary of State William Burns to discuss Syria.
On Thursday, British Foreign Secretary William Hague said world powers will have to step up their response to the conflict if the violence worsens, warning that all options were on the table.
He reiterated that Britain would seek to amend the EU weapons embargo on Syria when it comes up for review on March 1 to allow them to arm rebels opposed to Assad's regime.
In an update to the House of Commons, Hague said Britain was supporting Brahimi's efforts to end the conflict, and revealed the envoy would visit London for talks later this month.
Inside Syria, meanwhile, continued fighting drowned out the diplomatic tussling.
NATO said the Syrian army on Wednesday fired a short-range ballistic missile against rebel-held parts of the north, following similar launches last week.
In the Taftanaz airbase in northwestern Syria, regime warplanes launched raids to try to dislodge rebels who have seized more than half of the compound amid fierce clashes on the ground, a watchdog told AFP.
On Wednesday, 57 people were killed in violence across Syria, according to the Observatory, which relies on a network of activists and medics on the ground.