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. The aim of this study is to investigate the antifungal activity of clove oil extract against systemic induced infection In vivo by Candida albicans in mice. Fifty mice were used to induce systemic infection by injecting 1 ml of 1×106 C.albicans suspension intra-peritoneally for seven days consecutive, then sacrificed to observe the incidence of infection in internal organs (gross lesion) and measure the level of IL-6 and serum creatinine plus histopathological changes. The development of systemic infection with C. albicans (1 × 106 cells) was observed daily for 14 days which was accompanied with clinical signs of infection, including weight loss, depression, and ruffled appearance. IL-6 level showed no significant difference in all group before treatment and after inducing infection the level of IL-6 showed significant increase (P≤0.01) in control positive group while group treated with clove oil 5 mg/kg and 10 mg/kg showed significant decrease in the level compared with infected group and fluconazole treated group . Serum creatinine concentration was within the normal values in all groups (p>0.01) before the infection. There were an increase significantly (P≤0.01) in the level in all infected mice after 7 days of infection. The serum creatinine values of treated group with clove oil extract 5 mg/kg and 10 mg/kg showed decreased in the creatinine concentration . The present results demonstrated that the essential oil of clove extract rich with eugenol has great antifungal power. This extract can be suggested as antimicrobial and antifungal to treat candidemia and reduce the incidence of mortality rate due to systemic candidiasis.