Objectives: Silent information regulator 2-related enzymes (Sirtuin or SIRT) are the first discovered class III histone deacetylases. Our previous study has found that, one of its members, Sirtuin 6 is correlated with urinary albumin excretion rate in its circulating expression of type 2 diabetic patients [1]. Thus, the purpose of this study is to explore the expression of Sirtuin 6 in the kidneys. Methods: Renal tissues from SD rats were extracted and cortex, inner and outer medulla were separated. The target protein and mRNA in renal tissues were co-located by immunofluorescence and immunohistochemistry using multiple biomarkers. Semi-quantitative analysis was performed by molecular biology experiments. Results: Sirtuin 6 is mainly expressed in the cortical and proximal medullary nephron regions (Figure 1 and 2). The single cell sequencing in Figure 3 showed that the whole Sirtuin family expressed similar expressions in renal tissues, which may have similar physiological functions. The subcellular immunofluorescence in Figure 4 showed that Sirtuin 6 was mainly expressed in the nucleus, and partly in the cytoplasm. Moreover, there is a joint expression area with the endoplasmic reticulum that colored orange. Conclusions: Sirtuin 6 is mainly expressed in the cortex and the proximal medullary nephron, and is mainly expressed in the nucleus, and to a certain extent in the cytoplasm, especially in the endoplasmic reticulum. These findings have important implications for further study of the renal physiological function of the Sirtuin family.