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Background: Onosma hispidum (Ratanjot) belongs to the family Boraginaceae. The genus Onosma has about 150 known species in Asia. It has been found to be effective as an antioxidant, anti-inflammatory, and antimicrobial agent and promotes healing in burns, foot ulcers, and wounds. Aim: To study the effect of O. hispidum on blood glucose level in glucose-loaded, normal, and hyperglycemic rats. Settings: Department of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India. Design: An experimental study was designed. Materials and Methods: The methanolic root extracts of O. hispidum are compared with glibenclamide for their influence on fasting blood glucose in glucose-loaded, normoglycemic, and alloxan-induced (120 mg/kg i.p) hyperglycemic rats. Statistical Analysis: The data were analysed by one way analysis of variance followed by Dunnett's test (P < 0.01). Results: In glucose-loaded, normal and hyperglycemic rats, the methanolic root extract of O. hispidum at the dose of 100 mg/kg p.o. reduced blood glucose significantly as compared to control, and it was almost as effective as glibenclamide. Conclusion: The methanolic root extract of O. hispidum has hypoglycemic action. As diabetes is associated with hyperglycemia and several other pathological changes such as infections, inflammation, foot ulcers and impairment of wound healing, these additional effects besides hypoglycemic effect of O. hispidum may be proved as a breakthrough in the treatment of diabetes. Biochemical and receptor oriented molecular studies are required to find out the exact mechanism of hypoglycemic action of O. hispidum. [ABSTRACT FROM AUTHOR]