Epizootic Lymphangitis (EL) is a chronic debilitating disease of equines caused by Histoplasma capsulatum variety farciminosum (HCF). It is one of the major equine diseases with economics and equines welfare consequences. Rapid diagnostic tests and early treatment options helps the treatment, control and prevention of the disease. An experimental study design was conducted from Nov, 2019 to June, 2020 to assess the histofarcin skin test and evaluate antifungal efficacy of Crotonmacrostachyus against the mycelium form of HCF. In this study, the histofarcin antigen used for histofarcin skin test was prepared from field isolates of HCF, identified from clinical cases of EL in cart-mules from Bahir Dar town. Then, histofarcin skin test was evaluated on 60 mules, 15 clinically infected cases and 45 apparently healthy mules. Each mule was injected with 0.1ml of the histofarcin skin test antigen intradermally in the middle of the neck. The thickness of the skin was measured before injection and 24 hrs post injection using Bar Knight Mc Lintock (McLK- P0005) caliper. The sensitivity and specificity of histofarcin skin test was 100 % and 95%, respectively. An in vitro growth inhibitory effect of Croton macrostachyus against the mycelia form of HCF was evaluated. Two-fold serial dilutions of the methanol extracts of the plant were prepared and assessed. A culture media with no antifungal agent and media containing ketoconazole served as a negative and positive control, respectively. The results showed that Croton macrostachyus have inhibitory effect at concentrations ranging from 2.5mg/ml–10mg/ml. Thus, the minimum inhibitory concentration of the plant extract was found to be 2.5mg/ml. In conclusion, this study demonstrated that histofarcin skin test is a potential diagnostic tool for screening of EL. Also, the methanol extracts of Croton macrostachyus showed good in-vitro growth inhibitory activity against the mycelial phase of HCF. Therefore, Validation of histofarcin skin test assessment is necessary. Also, further investigation of the effects of C. macrostachyus on the yeast form of HCF is needed in addition to Phytochemial analysis (fractionation) and evaluation of the toxicity of the plant