Abstract: Objective To observe the expression of calcium-sensing receptor (CaSR) during the formation of renal calcium oxalate stones dynamically in rats and explore the role of CaSR in the formation of renal calcium oxalate stones in rats. Methods Sixty male Wistar rats were randomly divided into normal control group and calculi group, with 30 rats in each group. Rats in normal control group were treated with normal drinking water and normal saline (2 ml per day), while rats in calculi group were given 1% ethylene glycol and 2% ammonium chloride every day with 2 ml each day to establish Wistar rat calcium oxalate stone model. General conditions of rats were followed up for 10 weeks, then rats in each group (3 rats per week) were sacrificed to collect bilateral renal specimens. Light microscope and HE staining were used to observe the formation of renal calculus, and the expression level of CaSR in renal tissues was detected by immunohistochemical staining technique. Results From the third week onward, bright crystals were found in the kidney sections of the calculus rats, mainly distributed in distal convoluted tubules and proximal convoluted tubules.Slight expansion of renal tubules was seen in renal tissue. Occasionally, the epithelium of the renal tubule fell off or the interstitium of the kidney had lymphocytic infiltration. No pathological change was found in the renal tissue of the normal control group at 1-10 weeks. Immunohistochemistry results showed that in the fi rst two weeks, there was no significant difference in the staining degree of CaSR in the renal tissues between the two groups. From the third week, the degree of staining in CaSR localization in the renal tissue of calculi group increased significantly compared with the control group. Conclusion The high expression of CaSR may play an important role in the formation of renal calcium oxalate stones in rats.