This present study was undertaken to examine treating effects of St. John's Wort (SJW) extract on nociceptive perception of STZ-diabetic animals based on its potential antidiabetic and antinociceptive activities. One week administrations of SJW extract (125 and 250 mg/kg) induced significant decrease in high blood glucose levels of three weeks STZ-diabetic rats and improved their dysregulated metabolic parameters. In addition, SJW extract treatment caused restoration in the mechanical hyperalgesia of diabetic animals. These findings provide a rationale for the traditional use of SJW against diabetes and display the potential of this plant as a new drug candidate/source for the treatment of diabetic pain. (C) 2011 Elsevier B.V. All rights reserved.