6-O-β-D(+)-Glucose stearate serving as a model product of glucose fatty acid monoesters was synthesized using lipase B from Candida antarctica (Chirazyme® L-2) in a mainly solid-phase system in a stirred-tank membrane reactor. Esterification was performed in the presence of a small amount of ethyl methylketone (EMK), maintaining a catalytic liquid phase as well as forming an azeotrope with the reaction water. The azeotrope was evaporated and broken by membrane vapor permeation, then the dried EMK was returned to the reaction medium. The process was optimized by response surface methodology based on five major reaction parameters [time (Tr), substrate ratio (acyl donor to glucose, Sr), temperature (Rt), amount of solvent [solvent to substrates, [w/w], Sa), and enzyme load (El)] varied at three levels, resulting in higher yields. Thus, under optimized conditions [Tr = 58 h; Sr = 2.7; El= 8.9% (w/w); Rt = 78°.C; Sa = 1.9], up to 93% yields of glucose stearate were achieved.