OBJECTIVE: To investigate the effect of hydro-ethanolic extract of Zataria multiflora (Z. multiflora) on endothelin level, total and differential white blood cells (WBC) count of sensitized guinea pigs. METHODS: Five groups of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone (group S), drinking water containing three concentrations of Z. multiflora (0.2, 0.4 and 0.8 mg/mL as groups S+Z1, S+Z2 and S+Z3) and dexamethasone (group S+D), n=6 for each group. The endothelin levels as well as total and differential WBC count in blood of sensitized and control guinea pigs were evaluated using enzyme linked immunosorbent assay method, and hemocytometer and Wright-Giemsa's staining of blood sample smear respectively. RESULTS: Blood endothelin levels, total and most differential WBC count were increased but lymphocytes decreased in sensitized animals compared to controls (allP <0.01). In groups S+D, S+Z2 and S+Z3 endothelin level, total and differential WBC counts were significantly improved compared with group S (P <0.01). Although, all measured parameters in group S+Z1 was lower than group S+D (P <0.01), some parameters in group S+Z3 were greater than in group S+D (P <0.05 toP <0.01). CONCLUSION The results showed an anti-inflammatory effect of Z. multiflora extract in sensitized guinea pigs, which may suggest a therapeutic potential for the plant on asthma.