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Context: The clinical applications of well-known benzodiazepines as anxiolytic agents are limited because of their side effects. Therefore, the development of new pharmacological agents, from medicinal plants, is well justified. Objective: Among medicinal plants, Gelsemium sempervirens (L.) Aiton. (Loganiaceae) has been recommended for relief of anxiety in traditional folk medicines. Nevertheless, no pharmacological studies have so far evaluated it in this regard. The purpose of the present study was to investigate the anxiolytic effects of various extracts of the roots and rhizomes of G. sempervirens. Materials and methods: Petroleum ether, chloroform, methanol, and water extracts of G. sempervirens were prepared by successive extractions using a Soxhlet apparatus, and subsequently evaluated for antianxiety activity using the elevated plus maze model. Diazepam was used as standard drug. Results: Among various extracts, the methanol extract of G. sempervirens exhibited significant increases in open arm entries and mean time spent in open arms at the dosage of 150 mg/kg. A fraction (F9.4) derived from the methanol extract was also observed to exhibit significant anxiolytic activity at the dose level of 10 mg/kg in the elevated plus maze test. Conclusion: The present study clearly demonstrated that the methanol extract exerts an anxiolytic effect on mice, and it could serve as a new approach for the treatment of anxiety. [ABSTRACT FROM AUTHOR]