Holbrooke will meet Afghanistan's defence and interior ministers before holding talks with Karzai on Saturday, MacDonald said.
The US representative is also expected to discuss with Afghan leaders a Russian offer to open up new supply lines into Afghanistan for international forces following a string of attacks on existing routes.
Holbrooke's first visit to the country also comes amid fears that the security situation is deteriorating in and around Kabul after the Taliban launched one of their most audacious raids on the city to date on Wednesday, killing 20 people in a co-ordinated assault on three government buildings.
Afghan soldiers have been heavily deployed across the capital for Holbrooke's visit, which is part of a broader tour of the region.
Afghan intelligence officers say they are investigating links between Pakistan and Taliban fighters who carried out the raid.
|Supplies to international forces have been disrupted by Taliban attacks [AFP]
"As they were entering the ministry of justice before starting their indiscriminate killing of the civilians in there, [the attackers] sent three messages to Pakistan calling for the blessing of their mastermind," Amrullah Saleh, an Afghan intelligence chief, said.
Holbrooke could ask Afghan government leaders why they cannot even secure government infrastructure in the capital, MacDonald said.
"This is clearly something Holbrooke will be thinking of as he is not only responsible for Afghanistan, as far as the US is concerned, but also for Pakistan."
Resurgent Taliban fighters have carried out a series of raids and bomb attacks across Afghanistan in recent months.
Kabul has said that most of the opposition fighters are based in Pakistan's remote tribal regions to the east of Afghanistan.