Khan and his Movement for Justice Party, along with Western and local activists, began the drive Saturday in Islamabad.
The convoy is headed to the South Waziristan tribal district along the Afghan border, the target of frequent U.S. drone attacks.
VOA's Ayaz Gul, who joined the convoy, says protesters expressed their anti-American sentiment.
“You can see the anger. You can feel it. Even in the rally, most of the time the participants were chanting anti-American slogans and they were just condemning America.”
On Friday, a Pakistan Taliban spokesman said the group would not provide security for the motorcade and labeled Khan a Westernized and secular man.
Khan has dismissed concerns that the convoy could be attacked by the Taliban and other Islamist terrorists.
However, Gul says Khan is traveling in an armored vehicle and appears to be concerned about his safety.
“One could see that Imran Khan, himself, was pretty nervous because he was rarely stepping out of his vehicle even though this convoy was moving at a very slow pace. But, wherever he stopped, he would rarely come out of his car. His private security guards would not let anybody go close to him.”
Gul says less than 200 vehicles initially set off on the route but the number swelled to about 500 vehicles.
Drone strikes are a contentious issue between the U.S. and Pakistan. Islamabad says the strikes violate its sovereignty. The U.S. believes they are a key tool in the effort to defeat al-Qaida. VoA.