A non-dissolving pretreatment consisting in the direct contact of cellulose and the ionic liquid tetra(n-butyl)phosphonium acetate, or its fluid mixtures with other phosphonium ionic liquids or with molecular liquids such as ethanol or DMSO, causes a reduction in the crystallinity of the popular microcrystalline cellulose-type Avicel PH-101 under mild conditions. At the same time, the degree of polymerization and the thermal stability of the pretreated Avicel remain essentially unaltered with respect to the untreated Avicel. The diminution of the crystallinity has been related to the increase of the reactivity of the pretreated Avicel samples via analysis of the kinetics of their enzymatic hydrolysis. For selected samples, this improved reactivity has been confirmed through their effective carboxymethylation under a simplified and milder reaction procedure.