Shawkat is a brother-in-law of Bashar al-Assad, the president, and one of the top Syrian officials linked to the assassination of Rafiq al-Hariri, the former Lebanese prime minister, by the UN investigation into the bombing.
A Syrian official said in a statement: "This decision shows the extent of this administration's arrogant and unilateral practices in its attempts to impose its will on the international community,"
On Wednesday, the US Treasury Department ordered US banks to block any assets found in the US belonging to Shawkat.
Americans also are barred from doing business with him.
The department alleges that Shawkat has played a role in furthering Syria's "support for terrorism and interference in the sovereignty of Lebanon".
Policies against Arabs
The Syrian official, who was not named in keeping with government practice, said in the statement the US action "once again proves the US involvement in defending Israel's aggressive policies against the Arabs".
"The policies supported by the US administration do not serve security and stability in our region. But they would increase their rejection by the Arab people," the official said.
"This decision shows the extent of this administration's arrogant and unilateral practices in its attempts to impose
its will on the international community"
The US Treasury alleges that Shawkat had dealings with Lebanon's Hizb Allah fighters and Palestinian groups, the
Popular Front for the Liberation of Palestine-General Command, Hamas and Islamic Jihad - which the US has designated as global "terrorists".
Shawkat met officials from these groups and "discussed co-ordination and co-operation" among them, the department alleges.