Abstract: This review focuses on the efficacy and safety of Urtica dioica which has been utilized in traditional medicine for management of diabetes. All relevant databases including Pubmed, Google Scholar, Web of Science, Scopus, Iranmedex and MD Consult were searched for the terms diabetes mellitus and Urtica dioica without limitation up to 15th September 2010. All the animal studies with the outcome of change in blood glucose or other relevant complications of diabetes and all available abstracts were included. Review articles and letters to the editor were excluded. Search of databases resulted in 724 articles which 87 were potentially relevant studies on Urtica dioica and diabetes. On the basis of inclusion/exclusion criteria, 21 studies were finally included. One human and 20 animal studies were reviewed for the efficacy of Urtica dioica. Most of these studies showed significant decrease in blood glucose and complications of diabetes by use of Urtica dioica. Urtica dioica can affect both pancreatic and extra pancreatic pathways. Available evidences suggest that Urtica dioica can be used to treat diabetes and its long-term complications. Of course, further experiments would help determine exact mechanisms of action, effects and side effects of this herbal medicine.