A systematic investigation of the interaction of microwave irradiation with microcrystalline cellulose has been carried out, covering a broad temperature range (150 → 270°C). A variety of analytical techniques (e.g., HPLC, C NMR, FTIR, CHN analysis, hydrogen-deuterium exchange) allowed for the analysis of the obtained liquid and solid products. Based on these results a mechanism of cellulose interaction with microwaves is proposed. Thereby the degree of freedom of the cellulose enclosed CHOH groups was found to be crucial. This mechanism allows for the explanation of the different experimental observations such as high efficiency of microwave treatment; the dependence of the selectivity/yield of glucose on the applied microwave density; the observed high glucose to HMF ratio; and the influence of the degree of cellulose crystallinity on the results of the hydrolysis process. The highest selectivity toward glucose was found to be ∼75% while the highest glucose yield obtained was 21%.