In a recent episode of the show, Lexie and Jackson ended up in the shower together.
Speaking to Zap2It, Williams explained that he is expecting a mixed reaction from viewers of the show.
"It sounds like people are kind of keen about the idea and kind of interested about what's happening with Jackson and Lexie or 'Jack-xie', whatever the name is they make up for it," he said.
"But I would be surprised if there wasn't a little fallout from the Mark and Lexie lovers. That makes sense. Their relationship happened for a while, so it would be weird if people didn't care. They should care."
Meanwhile, Leigh suggested that the unhappy fans will just need some time to get used to the relationship.
"There's usually some kind of uproar about a new relationship or a relationship that happens in the wings or on the cusp of another one," she said. "So I think you [have] got to give it some time. Let it simmer. Let things marinate a little bit. And it could be surprising which way she goes and you might actually really like it and in true Grey's fashion it can all change tomorrow. Enjoy the ride!"
Grey's Anatomy airs on Thursday at 9/8c on ABC in the US and on Wednesday at 10pm on Sky Living in the UK.
> 'Grey's Anatomy' star teases love triangle