Abstract: Photoacoustic imaging technology based on laser-induced ultrasound mechanism combines the high contrast of optical imaging and the deep penetration of ultrasound imaging, which can reflect the distribution of endogenous absorbents in living organisms in a label-free and non-invasive way, especially suitable for real-time imaging of the whole brain of rodent models. In order to prove the application of photoacoustic imaging technology in brain science research and brain disease monitoring, a photoacoustic microscopic imaging system with spatial resolution of tens of microns and effective imaging depth of more than 1 mm was constructed. Taking APP/PS1 transgenic Alzheimer’s disease (AD) model mice and WT mice as research objects, the ability of photoacoustic imaging in characterizing the brain structure changes and vascular network of AD mice and WT mice was explored from three levels of brain tissue slices, in vitro whole brain and in vivo whole brain. It demonstrates the great potential of photoacoustic imaging technology in monitoring brain structural changes and cerebrovascular network characteristics during the development of brain diseases, which can provide deeper insights into many brain science studies and the development mechanism of neurodegenerative brain diseases.