The hard-throwing southpaw, who has been hit hard in three starts this season, experienced soreness in his knee following Friday's start against the Milwaukee Brewers, in which he was pounded for 10 runs over 4 2/3 innings.
Johnson, 39, underwent an MRI the following day that showed no damage to the knee. The swelling subsided before flaring up again after he threw in his normal bullpen session prior to Tuesday's game against the Rockies.
"We think that the best course of action is to get rid of that swelling and get rid of that inflammation before we run him back to the mound," said Arizona Manager Bob Brenly. "If he goes out there to pitch (Wednesday), chances are that thing will blow up like a balloon, so we will shut him down for a couple of days. He will probably throw a side session over the weekend to prepare for his start the 22nd in Montreal."
In three starts this season, Johnson is 0-2 with an 8.31 ERA.
"The Big Unit" has been ripped for 16 earned runs and 21 hits over 17 innings, and has not looked anything like baseball's most dominant pitcher.
Johnson, who missed one start last season with a sore back, will have his turn in the rotation taken by Miguel Batista.
Like Johnson, the two-time defending National League West champion Diamondbacks have struggled this season. They own the National League's worst record at 3-11.