Intoduction: The differences in protein expression of calcium sensitive receptor (CaSR) and claudin-14 in a kidney stone model established by nano bacteria (NB) and ethylene glycol (EG) were compared. Material and methods: Ninety Wistar male rats were randomly divided into the NB group, the EG group, and the blank control group (NC group), with 30 rats in each group. Three rats of each group were sacrificed every week after injection. Histopathology was used to evaluate the stone formation of each group. The expression of CaSR and claudin-14 protein was detected by immunohistochemistry every week. Results: There was formation of bright crystals in the kidneys of the EG group and the NB group, but not the NC group. At the 3rd week, the expression of CaSR and claudin-14 in the kidney tissue of the EG group began to increase while that in the NB group increased at the 4th week. The expression of CaSR and claudin-14 protein in the EG group was stronger than that in the NB group. Meanwhile, CaSR was expressed in the NC group but did not change significantly. Claudin-14 was not expressed in the NC group. Conclusions: Our results indicate that the traditional EG kidney stone modeling method is more rapid than the NB kidney stone modeling method, with a high stone formation rate, and the CaSR and claudin-14 protein expression levels are higher. Meanwhile, the NB used to establish the kidney stone model was isolated from patients with kidney stones, which may imitate the process of natural formation of kidney stones of patients. Therefore, the results of our research are more conducive to related research on the etiology of stones.