The in-demand forward has enlisted the help of lawyer Harro Knijff, who supported Ronald and Frank de Boer when they had a similar case against Ajax in 1998.
The 20-year-old has just signed a contract until 2011 with the Rotterdam club but is now eager to move to Spain.
"I can confirm that I am busy preparing the request for an arbitration case," Knijff told Sportweek magazine.
Feyenoord are determined to hold onto their prize asset though, and earlier this year rejected a reported 12.5-million-euro bid from the Spanish champions.
But there is every chance Drenthe will go once a club meets Feyenoord's undisclosed valuation.
"We regret that things are turning towards this," director Peter Vogelzang told the club website.
"We have made our standpoint public a few times already and nothing has changed in that: Feyenoord doesn't want to see Royston Drenthe go to another club.
"Our intention is to keep him at the club for at least one more year and if possible longer. We did not extend and renew his contract in April until the summer of 2011 for nothing.
"Feyenoord only wants to sell Drenthe if we get an offer that is as high as we think Royston Drenthe is worth to us."