Maqu County is located in southwest Gansu Province, which is an important part of the Qinghai Tibet Plateau, and is one of main water conservation districts of the Yellow River. Maqu alpine meadow is an important natural forage resource of China, and is key to the livelihood of local herdsmen. In recent years, desertification has become a serious threat to the ecosystem of Maqu alpine meadow due to the combined effects of anthropogenic and natural factors. The aim of this study was to investigate the effects of desertification on soil microbial biomass and enzyme activities in Maqu alpine meadow. According to the standard of desertification, we selected three types of desertification grade plots and one type of non-desertification plot in August 2013. Soil samples were collected from 0-20 cm depths of typical areas of these plots and were brought to the laboratory. The soil physical properties, soil microbial populations, and enzyme activities were determined, and the relationships between them in different desertification degrees were analyzed. The results were as follows:1) With the aggravation of the desertification degree of Maqu alpine meadow, the clay particle content, water content, invertase activity, urease activity, neutral phosphatase activity, and catalase activity in soil gradually decreased. At the same time, soil fine sand content and pH gradually increased, and coarse sand content, biomass of bacteria, fungi, actinomycetes, and total biomass of microorganisms increased first and then decreased. 2) In the desertification soil, the main microbial component was bacteria, followed by actinomycetes and fungi. The percentage of bacteria reached a maximum in the moderate desertification soil, and actinomycetes and fungi showed the maximum value in slight desertification soil. 3) During the desertification proceed of Maqu alpine meadow, the dominant factors driving the change in soil microorganism biomass were soil porosity and water content. The prime factors causing changes in soil enzyme activities were soil water content, porosity, pH, and flora and fauna in the early desertification soil, and soil microorganism, porosity, water content, and flora and fauna in the late desertification soil. Thus, desertification directly changed the soil particle composition and vegetation of Maqu alpine meadow, and indirectly changed the soil microbial populations. Therefore, the first task for restoring the Maqu alpine meadow ecosystem is to reverse desertification using biological and mechanical measures.