Three former heads of the central bank say the probe seeks to undermine the Fed's independence and "has no place" in the US.
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In a statement on Monday, 10 economic policy leaders - including four former Treasury Department secretaries - joined former Fed chairs Janet Yellen, Ben Bernanke and Alan Greenspan to rally behind Powell.
"The Federal Reserve's independence and the public's perception of that independence are critical for economic performance," they wrote.
The probe, they added, "has no place in the United States whose greatest strength is the rule of law, which is at the foundation of our economic success".
"This is how monetary policy is made in emerging markets with weak institutions, with highly negative consequences for inflation and the functioning of their economies more broadly," the former economic policy leaders said.
The signatories included former federal government officials appointed by both Democratic and Republican presidents.
The statement of condemnation was published one day after Powell disclosed that the US Department of Justice (DoJ) served the agency with subpoenas and threatened a criminal indictment over testimony he gave to a Senate committee about renovations to Federal Reserve buildings.
Powell, whose unscheduled video statement came as a highly unusual move, also called the investigation "unprecedented". He said he believed it stemmed from US President Donald Trump's anger over the Fed's setting of interest rates.
The DoJ probe "should be seen in the broader context of the administration's threats and ongoing pressure", Powell said.
Trump has publicly urged Powell to cut interest rates in order to reduce the US government's hefty borrowing costs and to make it easier for Americans to get mortgages and other loans.
Last year, Trump spent months at