Epizootic lymphangitis (EL) has deleterious effect on both welfare and health of the horses and mules so that it has a serious negative impact on the livelihoods of cart-horse owners/drivers in the affected parts of Ethiopia. Unfortunately, antifungal drugs for the treatment of epizootic lymphangitis are costly and mostly unavailable in such areas. The aim of this study was to investigate the effect of xanthium stramorium leaf extract (XSLE) on the growth of the mycelial form of histoplasma capsulatum var farciminosum which has been reported to have a strong antifungal activity in previous studies, in vitro. Histoplasma capsulatum var farciminosum was isolated from a horse with a cutaneous form of EL. Agar dilution assay was performed to evaluate the anti HCF activity of XSLE and measure the minimum inhibitory concentration (MIC). Ketoconazol was used as a positive control. Xanthium stramorium extract inhibited the growth of HCF at concentrations of 0.068 mg/ml. The result indicates that XSLE can potentially be used for the treatment of EL provided that convenient methods of preparation, dose and route of administration are established through rigorous in vitro trials.