© S Sabawoon/EPALeon Panetta in Kabul, where he called on Pakistan to do more to crack down on militants.
In some of the strongest language used by a US official to describe the strained ties between Washington and Islamabad, Panetta said: "It is difficult to achieve peace in Afghanistan as long as there is a safe haven for terrorists in Pakistan."
Panetta arrived in Kabul on Thursday morning for talks with Nato military leaders amid rising violence in the war against the Taliban and a spate of deadly attacks, including a Nato air strike said to have killed 18 villagers.
"It is very important for Pakistan to take steps. It is an increasing concern, the issue of safe havens, and we are reaching the limits of our patience," he told reporters.
The United States has long pushed Pakistan to do more to help in the war against militancy, but the relationship has received a series of blows, not least by a unilateral US raid into Pakistan to kill Osama bin Laden last year that humiliated Islamabad.
Panetta also urged Pakistan to go after the Haqqani militant network, one of the US's most feared enemies in Afghanistan, and said Washington would exert diplomatic pressure and take any other steps needed to protect its forces.
"It is an increasing concern that safe havens exist, and those like the Haqqanis make use of that to attack our forces," he said.
"We are reaching the limits of our patience for that reason. It is extremely important for Pakistan to take action to prevent [giving] the Haqqanis safe havens, and for terrorists to use their country as a safety net to conduct attacks on our forces."
The comments came as Washington appeared to be looking to other allies in the region for help in the face of Pakistan's foot-dragging. Panetta arrived in Kabul after a visit to India, Pakistan's old enemy, where he urged New Delhi to take a more active role in Afghanistan.
Nato has signed an agreement with three countries to the north of Afghanistan for land routes as the alliance begins a withdrawal of its forces from the country next year.
The Nato chief, Anders Fogh Rasmussen, said earlier this week the "reverse transit" deal had been signed with Uzbekistan, Kazakhstan and Kyrgyzstan.
Pakistan closed the shorter and cheaper routes through its territory last year to protest against a cross-border Nato air attack that killed 24 Pakistani soldiers. Discussions to reopen the Pakistan routes have stalled.
Talk of sanctioning Pakistan, who has already cut off overland supply and retreat routes, leaves only the 3 nations to the North, thence through Russia.
That's not a pretty picture, but it is a bed that was made and must now be lain in.