Opioid tolerance isa primary problem which hampers opioids to treat acute and chronic pain. The mechanism of opioid tolerance is complex and is associated with many regulatory factors. Recent studies indicate that glucocorticoid receptors play regulatory role in each link of mechanism of opioid tolerance. It would be beneficial for treatment of intractable pain to find out the methods to treat opioid tolerance by utilizing the regulatory effect of glucocorticoid receptors on opioid tolerance.