Objective To evaluate the therapeutic effect of modifiedHuanglian-Jiedudecoction for resistant hypertension and explore its possible mechanism.Methods A total of 90 patients with resistant hypertension were recruited and randomly divided into a treatment group and a control group, 45 patients in each group. The control group was treated with oral administration of irbesartan and hydrochlorothiazide tablets and controlled-release nifedipine tablets, while the treatment group was further added modifiedHuanglian-Jiedu decoction for 4 weeks. Plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) were measured by radioimmunoassay.Rusults The total efficiency according to the TCM syndrome in the treatment group was 86.7%(39/45) which was higher than 64.4%(29/45) in the control group(χ2=4.873,P=0.027). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased after the treatment in both groups ( SBP in the treatment group: 119.26 ± 9.34 mmHgvs.172.11 ± 10.52 mmHg,t=25.201,P<0.01; DBP in the treatment group: 78.18 ± 7.21 mmHgvs.111.12 ± 11.16 mmHg,t=16.631, P<0.01; SBP in the control group: 145.21 ± 7.56 mmHgvs.171.32 ± 11.15 mmHg,t=13.002,P<0.01; DBP in the control group: 93.57±8.13 mmHgvs. 109.89 ± 12.21 mmHg,t=7.463,P<0.01), while the decrease of SBP (t=14.487,P<0.01) and DBP (t=9.501, P<0.01) in the treatment group was more greater than those in the control group. The control rate of blood pressure in the treatment and control groups were 73.3% (33/45) and 55.6% (25/45), respectively, there had no significant difference (χ2=2.376,P=0.123). The plasma ET in the treatment group was significantly decreased than that in the control group (75.68 ± 10.67 ng/Lvs.112.79 ± 12.26ng/L;t=15.317,P<0.05), and CGRP significantly increased (49.87 ± 4.75 ng/Lvs.33.87 ± 7.89 ng/L;t=11.654,P<0.05).Conclusion Modified Huanglian-Jiedudecoction may have some therapeutic effect for resistant hypertension, its mechanism may be involved in ET decreasing and CGRP increasing.