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Ephrem Ashenafi,1 Teferra Abula,1 Solomon Mequanente Abay,1 Mahlet Arayaselassie,2 Samson Taye,3 Rekik Ashebir Muluye3 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Pathology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Biomedical Research Team, Traditional and Modern Medicine Research Directorate, Ethiopian Public Health Institute, Addis Ababa, EthiopiaCorrespondence: Ephrem Ashenafi, Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia, Email ephremashenafiz@gmail.comBackground: The leaves of V. auriculifera has been used traditionally for the treatment of inflammatory disorders, and pain in various parts of Ethiopia. However, to our knowledge, the analgesic and anti-inflammatory activity of the crude extract and solvent fractions has never been experimentally studied.Objective: To assess the analgesic and anti-inflammatory activities of V. auriculifera leaf extract and solvent fractions in rodent models.Material and methods: Air-dried leaves of V. auriculifera were grounded and macerated using 80% methanol. The air-dried, grounded leaves were also successively extracted with ethyl acetate, and methanol. The residue was then macerated in water for 72 hr. The extract’s peripheral analgesic activity, as well as the solvent fractions, were determined using an acetic acid-induced writhing test. The hot plate model was used to assess the central analgesic effect. Carrageenan-induced hind paw edema and cotton pellet-induced granuloma models were used to assess the anti-inflammatory effect in rats.Results: The 80% methanol leaf extract and solvent fractions have demonstrated significant (p < 0.05) peripheral and central analgesic activity. Both 80% methanol leaf extract and solvent fractions of