The 29-year-old Briton, who won gold in the heptathlon at the London 2012 Olympics, gave birth to a son last year and made her last appearance at London's Anniversary Games in July 2013 when she finished fourth in the 100 hurdles.
Ennis-Hill will line up at the Manchester street event on May 9 as she begins her preparations for the Rio Olympics in 2016.
"I'm really looking forward to making my competitive return. The atmosphere in Manchester is always amazing," she said.
(Reporting by Michael Hann, editing by Tony Jimenez)
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