Introduction: Fungal infection is a serious health problem, involved with the life threatening mycosis and mortality. Emerging of resistance and limited antifungal drugs against most antifungal agents lead to the requirement for development of effective and alternate strategies to fight fungal infections, like herbal medicine such as clove oil which is used as antifungal agent against different strains like Candida albicans. Objective: In vivo investigation of antifungal activity of clove oil extract against  topical induced infection by Candida albicans in mice. Methods: Forty  mice were used to induce  skin infection by making a scratch  until the skin injuries was formed then  inoculate  1×10⁶  C.albicans suspension on scratched skin. Then observe the gross lesion, measure the level of IL-6 and histopathological changes. Result: The development of lesions in mice after induced  infection with C.albicans required a period of 5 days in all infected groups.  Group treated with clove oil 5 mg/ml showed absence of lesion at day 4 and return to normal thickness and regrowth of hair at day 7 of treatment with significant decrease in  level of IL-6 compared to group treated with clotrimazole 2%, which showed presence of dark patch on infected area at day 4 and return to normal but without regrowth of hair at day 7 with decrease in IL-6 but still high compared to negative control. Conclusion: Eugenol has  a strong activity against C. albicans in vivo. So, has potential therapeutic effect.