Trainer Doug O'Neill said the injury doesn't appear to be career-threatening but has been a concern for three months. A flare-up of the injury Tuesday led horse owner Paul Reddam to hold Square Eddie out of the derby.
"He's been adamant all along to err on the side of caution," O'Neill told The Courier-Journal newspaper in Louisville, Ky., of Reddam.
"The shin has been ice cold and sound and (Tuesday) he had a little heat in there. That's the first sign of some possible trouble."
Square Eddie has had eight starts, winning twice while finishing second three times and third twice. One of the second-place finishes was in last year's Breeders' Cup Juvenile. The horse has career winnings $817,366.
Square Eddie is the second horse in as many days to be withdrawn from Saturday's 135th Kentucky Derby. Quality Road, which had been the third favorite in betting lines, was taken from the race due to a quarter-crack injury to its right front hoof.