The CIA-operated spy plane targeted a house in Chashma Pul area of Miranshah, the main town of North Waziristan Agency, early this morning.
Four suspected militants in the house were killed instantly and two others injured. Local residents said several drones were seen hovering over the area after the attack.
Rehman, the deputy chief of Tehrik-e-Taliban Pakistan, was among the dead, security officials told journalists in the northwest.
However, a Taliban spokesman told news channels that the report of Rehman's death was "false".
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The development could not be independently confirmed as most of North Waziristan is controlled by Taliban warlords.
This was the first missile strike since Pakistan's landmark general elections on May 11 and the announcement of a new policy for the use of drones by President Barack Obama.
According to the new policy, drone strikes can only be used to prevent imminent attacks, when the capture of a suspect is not feasible and if there is a "near certainty" that civilians will not be killed.
"The government of Pakistan has consistently maintained that the drone strikes are counter-productive, entail loss of innocent civilian lives, have human rights and humanitarian implications and violate the principles of national sovereignty, territorial integrity and international law," the statement said.
Pakistan's general election was won by the PML-N and Prime Minister-elect Nawaz Sharif, set to assume office in June, has said Washington must take Islamabad's concerns about drone strikes seriously.
Foreign Secretary Jalil Abbas Jilani said on Friday that the drone strikes were illegal and counter-productive despite the new guidelines unveiled by Obama.