Impaired wound healing may cause economic and social problems and seriously reduce the quality of life. The uses of herbal medicines as new alternative treatments are under investigation. This study investigated the effect of Glycyrrhiza glabra L. extract on the full-thickness wound healing in Guinea Pig model. Eight male Guinea Pigs (700-800 g) were used to be creared a square full-thickness wound with 1.5 ×1.5 dimensions on the lumbodorsal area. The wounds were randomly divided into four groups: I; control, II; 1% phenytoin, III; 5% G. glabra and IV; 10 % G.glabra. On day 3, 5, 7, 9 and 12, wound size was measured for assessment of the percent of wound healing. In order to determine the wound healing activity, excisional biopsies were evaluated histopathologically on the 12th days of treatments. Acute inflammation, granulation tissue fibroblast maturation, collagen deposition, epidermal layer formation, neovascularization, keratin layer formation were evaluated according to the Abramov score method. Hydroalcoholic extract of G.glabra exhibited total phenolic and flavonoid contents of 114.1 ± 5.45 and 82.85 ± 6.38 mg, respectively. G.glabra creams (5% and 10% w/w)were significantly increased the epidermal formation, collagen deposition and neovascularization, and was decreased acute inflammation in comparison to the control group. Wound healing rate were increased in the G. glabra groups. G.glabra creams 10 % was more effective than 5% w/w. Our findings proved that 5% and 10% w/w G. glabra creams were effective in acute dermal wound healing. More studies with different doses of G. glabra extract are recommended.