Aim To explore the response and depressor of calcitonin gene-related peptide (CGRP) in the early phase of the 2-kindney, 1-clip Goldblatt hypertensive rats (2K1C), and the changes of treatment with perindopril or prazosin in this phase. Methods The 2K1C hypertensive rats were developed by part clipping the left renal artery. The plasma concentration of angiotensin Ⅱ and CGRP were determined by radioimmunoassay. CGRP mRNA expression was determined by reverse-transcription polymerase chain reaction (RT-PCR). Results The level of CGRP in plasma significantly increased compared with control groups (p<0.01). Perindopril significantly decreased the blood pressure concomitantly with an increase in the plasma concentration of CGRP and the expression of CGRP mRNA in dorsal root ganglia (DRG) in the 2K1C Goldblatt rats. Prazosin caused a hypotensive effect compared with 2K1C rats. Conclusions These results suggest that the 2K1C Goldblatt model exhibits a compensatory increase of sensory nerve actions, and that the depressor effects of perindopril may be related to stimulation of the synthesis and release of CGRP in the 2K1C Goldblatt hypertensive rats.