The showrunner told the Los Angeles Times that there is no romantic element to the friendship between Rizzoli (Angie Harmon) and Isles (Sasha Alexander).
"[We have] two gorgeous actresses together who have great, natural chemistry," she argued.
"[But they] are straight women who don't fear the interest in or the speculation about their relationship."
Alexander agreed that the crime-fighting pair are simply "friends and colleagues".
"Women in the workplace are often portrayed as catty and competitive," she suggested. "It's rare that you get to see them as smart friends and colleagues who can debate and disagree. They don't have to always sabotage each other and fall for the same guy."
Co-star Harmon added: "I hate to disappoint, but these characters are straight. If we lose viewers because of it, [then we're] sorry!"
Chris Vance, Colin Egglesfield, Jacqueline Bisset, Ed Begley Jr and Bill O'Reilly have already signed up for roles in the second season of Rizzoli & Isles.
The show returns to TNT on Monday, July 11 at 10/9c.
Watch a clip from the first season of Rizzoi & Isles below: