© 2021, Romanian Society for Pharmaceutical Sciences. All rights reserved.Inflammation is a natural response of the body's immune system to various external stimuli, in which the production of cytokines, nitric oxide, malondialdehyde (MDA) and myeloperoxidase (MPO) is enhanced. Glabridin is known for decreasing cell migration and increasing cGMP level. But so far, the anti-inflammatory effect of glabridin has not been proven histologically, and also its effect on oxidative stress parameters and cytokine levels has not been fully elucidated. The aim of this study, therefore, is to reveal possible mechanisms that can mediate the anti-inflammatory activity of glabridin. Animal groups were used including saline control, carrageenan, glabridin. Carrageenan was administered intraplantarly except for the saline control group. Paw thickness was measured at 0, 1, 2, 3 and 4 h which correspond to peak oedema times. MPO activity, MDA concentration, and glutathione (GSH) level in paw tissue for oxidant/antioxidant balance assessment were measured. Carrageenan increased the oedema, MDA, MPO, TNF‐α and IL-1β production, which were abolished by glabridin. In the dermis and hypodermis, carrageenan caused an increase in inflammatory cells. Glabridin has played an important role in preventing peripheral inflammation, and in the near future, targeting the peripheral anti-inflammatory effect as a promising alternative to treat inflammation diseases may be considered a novel pharmacologic approach.