Objective To investigate the relationship between the expression of vitamin D receptor (VDR) and calcium-sensing receptor receptor (CaSR) and the proliferative activity in the parathyroid tissue from secondary hyperparathyroidism (SHPT) patients. Methods The numbers of VDR- and CaSR-positive cells after immunohistochemistry staining in the parathyroid tissues of various degrees of SHPT were compared with those in the normal parathyroid tissues. Results Among the 21 proliferation parathyroid glands, one was diagnosed as diffuse hyperplasia (group B), 13 were diagnosed as nodular hyperplasia (group C), and 7 as adenoma hyperplasia (group D). (a) VDR was mostly nuclear localized in cells of normal parathyroid (group A). The expression of VDR in groups A, B, C and D was 78.0±2.5%, 57.1%, 31.0±6.7% and 23.0±2.1%, respectively (P＜0.001). The expression level of VDR correlated with the hyperplasia degree of parathyroid glands. (b) CaSR was mostly expressed on cell membrane and in cytoplasm. CaSR expression was reduced in parathyroid samples from SHPT patients (48.0±17.9%), as compared with that in group A (79.0±1.0%, P＜0.01). CaSR expression was 51%, 47.0±9.8% and 29.0±10.1% in group B, C and D, respectively (P＜0.01). Conclusions (a) The lower expression of VDR and CaSR appears to be the cause of SHPT refractory to the calcitrol pulse therapy. (b) Attempts to increase the expression of the two receptors or to use the agonists of the two receptors may be the new approaches to SHPT therapy.