The Gossip Girl star already has a two-year-old son with her husband, businessman Daniel Giersch.
The addition to the family will see the 40-year-old emulating the character she plays on the CW drama, mother-of-two Lily van Der Woodsen.
Rutherford told Us magazine that her toddler Hermes, who she sometimes takes to work, has bonded with all the cast.
"We have such a nice set because people bring their kids and their dogs. It looks like we're running a doggy daycare in the make-up room, it's really something," she said.
Rutherford, who also played Megan Lewis Mancini in Melrose Place during the 1990s, married Giersch in August 2006.