Al-Qaeda's number two Ayman al-Zawahiri has appeared in a video saying that Iraqi insurgents have "broken the back" of the US military.
He praised "martyrdom operations" carried out by al-Qaeda in Iraq in the video, posted on an Islamist website.
And he called on the people and army of Pakistan to fight against President Musharraf's administration.
This is the third message from prominent al-Qaeda leaders to emerge within a week.
A tape from Osama Bin Laden was broadcast on 23 April, followed two days later by a message from Iraqi insurgent Abu Musab al-Zarqawi.
Zawahiri, who wore a black turban and a white robe in the video, described the leaders of Egypt, Jordan, Saudi Arabia and Iraq as traitors, and urged Muslims to "confront them".
He praised Iraqi militants, saying that the US, Britain and allies had "achieved nothing but losses, disasters and misfortunes" in Iraq.
"Al-Qaeda in Iraq alone has carried out 800 martyrdom operations in three years, besides the victories of the other mujahideen," he said. "This is what has broken the back of America in Iraq."
But the bulk of the 16-minute video, which was entitled "A message to the people of Pakistan", targeted President Musharraf.
"Every soldier and officer in the Pakistani military should know that Musharraf is throwing them into the burner of civil war in return for the bribes he is getting from the United States," said Zawahiri.
He urged Pakistanis "to remove this traitor from power" and told soldiers to disobey the orders of their commanders "to kill Muslims in Pakistan or Afghanistan".
Egyptian-born Zawahiri is regarded as Bin Laden's right-hand man.
The two have evaded capture since US-led forces brought down the Taleban regime in Afghanistan in 2001 following the September 2001 attacks on the US.