Background Opioids are the most powerful analgesics for the treatment of moderate to severe pain. Although opioids have analgesia effect, they have many side effects at the same time. Long term opioids exposure can induce hyperalgesia and tolerance. Increasing the dose of opioids, paradoxically, aggravate the hyperalgesia and tolerance, as a vicious cycle. The use of opioids, therefore, is largely limited in the clinical work. Purpose The relevant literatures which argue that δ-opioid receptors played an important role in the attenuation of opioid induced hyperalgesia（OIH） in recent years were summarized to help wide readership to stay up on the latest issues and trends at abroad. Content The structure, distribution, physiological function and the progress of antihyperalgesic effect of δ-opioid receptors were reviewed in this article. Those researches suggest that OIH and tolerance can be attenuated by the inhibition of δ-opioid receptor phosphorylation, knocking out δ-opioid receptor coding genes and the application of δ-opioid receptor antagonists. Trend With more scholars obtain a consensus on the antihyperalgesia effect of δ-opioid receptor,δ- opioid receptor may become a new target to treat pain in the clinical work.