High blood pressure is a major cause of stroke and cardiovascular complications. The development of a hypertensive crisis model allows rapid testing of the effects of antihypertensive drugs, meeting the need for research and development of chronic pharmacological models. A model of acute hypertension was induced by intraperitoneal injections of xylometazoline at different doses and subcutaneous injections of atropine at a dose of 0.4 mg/kg. This study applied the CODA high-throughput hypertensive machine to determine a suitable model. The results of injecting xylometazoline at a dose of 1 mg/kg ( IP) and atropine (0.4 mg/kg) (SC) showed induced hypertension with systolic >130 mmHg constantly with 15 circles in 20 minutes. The hypotensive effect was found when oral administration of nifedipine (6 mg/kg), losartan (100 mg/kg), and captopril (100 mg/kg). However, the hypotensive effect of bisoprolol was not found at a dose of 50 mg/kg. This mouse model can be applied for further screening and evaluating the therapeutic effect of hypotensive drugs.