Wolves were once hunted to near extinction in Europe, but in the 1950s countries began granting them protected status. Now populations are growing in several regions.
"The concentration of wolf packs in some European regions has become a real danger for livestock and potentially also for humans," von der Leyen said.
The president of the European Commission has personal experience of the alleged threat posed by wolves.
In September last year, a wolf crept into a paddock on the family's rural property in northern Germany and killed her beloved elderly pony Dolly.
Conservationists, however, have hailed the return of healthier wolf populations to Europe's mountains and forests, seeing the large predator as part of the natural food chain.
Under the EU Habitat Directive, first adopted in 1992, the wolf enjoys protected status.
But local and national exceptions to the law are possible, and von der Leyen urged "authorities to take action where necessary", adding: "Indeed, current EU legislation already enables them to do so."
Her statement urged local communities, scientists and officials to submit data on wolf numbers and their impact to a European Commission email address by September 22.
Using this information, the commission will then decide how to modify wolf protection laws "to introduce, where necessary, further flexibility".
The European Commission's announcement received angry comments from animal lovers on social media, many pointing out there have been no fatal attacks on humans by wolves in Europe for decades.
- 'Brave and clear' -
But major European member state governments are thinking along the same lines as Brussels -- as are some political parties keen to court rural voters angered by environmental protection laws.
German environment minister Steffi Lemke plans to put forward proposals to make it easier to shoot wolves that have attacked livestock.
"The shooting of wolves after their attacks must be made possible more swiftly and unbureaucratically," Lemke told Welt daily, adding that she will present her plans at the end of September.
"It is a tragedy for every livestock farmer and a great burden for those affected when dozens of sheep that have been ripped apart are lying on the pasture," said the Green Party politician.
French agriculture minister Marc Fesneau thanked von der Leyen for taking a "brave and clear" stance on the issue, urging European authorities to "advance with pragmatism".
While the rules had been introduced to protect an endangered species, he said, "now it is the farmers and their business that are in danger".
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