Ethnopharmacological relevance: Citrus limetta Risso (Rutaceae) is widely used in Mexico for healing purposes, among them as antihypertensive treatment. Aim of the study: To assess the antihypertensive effect of C. limetta leaves as one of its ethnomedical uses. Materials and methods: The acute response of blood pressure to angiotensin II administration was measured in mice. Additionally, the acute oral toxicity profiles were determined. Results: The findings of the current investigation showed that different concentrations of the aqueous extract prevented the raise of systolic blood pressure (p< or =0.001 vs. vehicle), diastolic blood pressure (p< or =0.0002 vs. vehicle) and mean blood pressure (p< or =0.0000 vs. vehicle); with a dose dependent effect for diastolic pressures at 125-500mg/kg dosages. The 500 and 1000mg/kg doses inhibited the action of Ang II in similar extent to telmisartan. Toxic signs or deaths were not observed in mice treated at 2000mg/kg of C. limetta extract. Conclusions: All doses of C. limetta aqueous extract, used in this assay, were safe and effective.