Abstract: In the past two decades, small animal neuroimaging study has been emerging as a powerful tool to investigate mechanism and treatment of many neurodegenerative diseases. With its non-invasive, region by region measurement capability and tomographic nature, neuroimaging techniques add significantly more values to the study of the transgenic/disease animal models for the understanding of the disease mechanism and the evaluation of potential treatments. The mouse has become a key animal model to study human diseases. The need for a standard template on atlas space becomes urgent and critical for mouse neuroimaging study. The aim of this research is to construct a framework which incorporates the anatomical template and atlas information into the computational neuroanatomy of the mouse brain. The template and atlas based framework developed in this research, which integrate characteristics of the atlas, variability of the average template and a group of well developed toolboxes, will provide maximum flexibility and robust performance for mouse data analysis. It is believed that this research will greatly facilitate the non-invasive mouse brain morphometry study. In summary, the study was composed of 4 main research areas: (1) low dimensional inter-subject mouse brain registration and high dimensional inter-subject mouse brain registration using Statistical Parametric Mapping (SPM); (2) mouse brain template and atlas framework construction; (3) mouse template toolboxes (MTT); and (4) the validity of the mouse brain template and atlas framework. The success of this research created an important imaging framework that can bridge the gap between studies in persons and laboratory animals, and established an indicator of diseases which could help screen candidate treatments and clarify disease mechanisms in both preclinical and clinical settings.