Objective:To evaluate the berries of Phytolacca dodecandra (P. dodecandra) for its effect on Histoplasma capsulatum var. farciminosum (HCF) and for the treatment of cases of epizootic lymphangitis (EL). Methods:Samples were collected from un-ruptured nodules of cases of EL at Debre Zeit and Akaki (central Ethiopia). Mycological culture and isolation of HCF were performed at the Aklilu Lemma Institute of Pathobiology. Phytochemical screening was done for n-butanol extract of P. dodecandra to detect alkaloids, saponins, phenolic compounds and flavonoids. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of aqueous and n-butanol extracts of P. dodecandra against HCF were determined by agar dilution assay. For the in vivo trial, 5%simple ointment was prepared from n-butanol extract and applied topically to 24 (twelve early and twelve moderate) cases of EL. Results:Phytochemical screening showed that n-butanol extract of P. dodecandra was positive for alkaloids, saponins and phenolic compounds but negative for flavonoids. The MICs of n-butanol and aqueous extracts of P. dodecandra were (0.039%-0.078%) and (0.625%-1.250%), respectively. The MFCs of n-butanol and aqueous extracts of P. dodecandra were (0.078%-0.156%) and (1.250%-2.500%), respectively. The MIC and MFC of ketoconazole (positive control) was (1.200×10-5%-2.500×10-5%) and (5.000×10-5%-1.000×10-4%), respectively while growth was observed on free medium (negative control). From the total of 24 treated cases of EL, 14 (58.3%) responded to treatment;however, 10 (41.7%) did not respond to treatment. There was no significant difference in the degree of response to treatment between early and moderate cases (χ2=0.686;P=0.408). Conclusions:It can be concluded that n-butanol extract of P. dodecandra demonstrates antifungal effects while the aqueous extract shows no antifungal activity.