Monodisperse carboxymethyl cellulose containing phenolic groups (CMC-Ph) microdroplets with a radius of 100–400 μm and a coefficient of variation below 3% were produced in a coflowing microfluidic device. The CMC-Ph solution containing horseradish peroxidase was used as the disperse phase and liquid paraffin containing H2O2 and lecithin as the continuous phase. The size of microdroplets decreased with the decreasing diameter of the inner channel and concentration of the disperse phase. When using a 0.04% CMC-Ph solution and the device with the inner diameter of 160 μm, the size of the microdroplets can be further controlled by the flow rates of both the continuous phase and disperse phase following exponential models. The volume of the microdroplet was not inversely proportional to the flow-rate ratio of the continuous phase to the disperse phase. There was a weak dependence of the volume on the flow of the continuous phase. The monodisperse microparticles possessed potential application for sensor, drug delivery system, cell encapsulation, catalysis, and imaging. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40663.