【Abstract】 Objectives The NAD-dependent deacetylase SIRT1 appears to have evolved complex roles in central nervous system. Recent studies suggest that SIRT1 has been involved in the processes of glucose and insulin secretion. The aim of the present study is to investigate if SIRT1 co-locates with IR in the adult C57BL/6 mice brain, which may provide morphological evidence for inherent relationship between SIRT1 and IR in brain. Methods Using double immunofluorescence staining to investigate if SIRT1 co-locates with IR and the distribution in the brain. Results SIRT1 immunoreactivity was mainly observed in the hippocampal CA1 pyramidal cells. The co-location analysis showed that SIRT1 was co-located with IR in the hippocampus, cortex and hypothalamus of adult mouse brain. In vitro, insulin regulated the expression of SIRT1. Conclusions SIRT1 was rich in neuron and collocated with IR. The results provide a morphological clue to explain the role of SIRT1 and IR in the brain function and neurological disorders.