AIM: To investigate the effect of FXR gene knockout on the kidney of mice. METHODS: Renal tubular epithelial cell-specific FXR gene knockout mice were constructed based on the cre-loxp system. qRT-PCR was used to detect the mRNA transcription level of FXR in kidney, western blot and immunofluorescence were used to detect the expression of FXR protein in kidney, hematoxylin-eosin staining and periodate sherff staining were used to observe the kidney morphology of mice, and transmission electron microscopy was used to observe the tubule morphology under ultrastructure. Renal function was assessed by testing Scr, BUN, and urine NAG. RESULTS: The mRNA transcription level and protein expression level of FXR in the renal tubular epithelial cells were decreased after specific knockout of FXR in mice, and there were obvious vacuolization in the renal tubules. The levels of SCr and BUN in the serum were not significantly changed, but the level of NAG in urine was increased. CONCLUSION: The mouse model of FXR gene knockout in renal tubular epithelial cells has been successfully established, and FXR knockout leads to vacuolization of renal tubular epithelial cells and impairment of renal function.