The actress, 53, who has played Jean Slater for eight years, will finish filming this week. Her last episode will air in October.
In a statement released by the star, she described her experience as "a huge privilege."
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"I treasure the viewer's care and love for the character not only through her hard times but through all the laughter too," she added.
"I will miss EastEnders enormously, but it is time for me to step back and enjoy other acting challenges."
Gillian has indicated she would like to return to the show in the future and has asked not to be killed off.
"I would love Jean to return to The Square one day, so let's hope this is not goodbye, but au revoir," she said.
Gillian’s departure follows the resignation of executive producer Lorraine Newman yesterday and puts more pressure on soap bosses who fear an exodus.
On her time in the show, Gillian worked closely with on-screen daughter Stacey, played by Lacey Turner, who left in 2010.
EastEnders has suffered a dip in ratings during the first half of 2013 and it is reported that show bosses fear Gillian's exit may be the first of many.
"Bosses need to turn things around fast. This summer is a critical time for EastEnders," a source told the Mirror.
Last Tuesday saw just 4.8 million viewers tune in, compared to 5.4 million who switched on Emmerdale.
It is rumoured the soap has splashed £1million on a dramatic crash scene involving one of the soap's favourite characters to draw audiences.
Phil Mitchell will be left fighting for his life after being involved in the accident with Carl White.
This summer's viewing will also include the return of Peggy Mitchell, played by Barbara Windsor, as well as Samantha Womack, reprising her role as Ronnie Mitchell.
Speaking of her return earlier this month, Samantha revealed, "I can't wait to be a Mitchell once again."