This paper describes the first experience for Uzbekistan in mammals' fauna inventory in the context of large administrative districts. Tashkent region was chosen as a model territory for researching – as an integral natural area with natural geographical boundaries. A revision of the composition and assessment of the fauna current conditions of economically significant mammals of this region was carried out. The primary limiting factors and threats to the existence of these species were analyzed. The permissible standards for the removal of economically significant mammalian species from the natural environment were determined, based on the data of the abundance and their habitats conditions. Standard approaches and methods for inventory have been developed: data collection and storage; working with sources of existing information; field research as the gaps closing basic method. Based on the results of the research, standard species profiles were prepared for 17 economically significant mammalian species, including data on distribution, landscape location, abundance, and permissible operational loads. A proposal to change the current conservation status of the Long-tailed Marmot, Corsac Fox and Steppe Polecat was justified. These species were previously considered as hunting objects, but now they have become rare. The impact of introduced and invasive species – Coypu, Muskrat, American Mink and Norway Rat on the native fauna was determined. The analysis of negative impacts on the species allowed to recommend a number of applied measures for the sustainable use of biological resources.