Matthews courted controversy in the opening match of the season between the two sides when he tackled Colin Kaepernick while out of bounds having stated before the match that he would target the 49ers quarterback.
His actions led Harbaugh to claim that Matthews was too intent on being viewed as a "tough guy", but McCarthy rubbished accusations that the Pro Bowler is a dirty player.
"Clay Matthews is not a dirty player, by no means. I addressed Harbaugh's comments in the team meeting and as always we'll stay above it," McCarthy told reporters.
The 49ers went on to win the match 34-28, with Kaepernick throwing three touchdown passes, including one on the play immediately following Matthews's illegal hit.