Silybin is widely used as a therapeutic agent for a variety of acute and chronic liver diseases. However, its application is limited by its extremely poor aqueous solubility, which results in poor oral absorption and bioavailability. In this work, silybin nanodispersion with high dissolution rate was prepared by using T-shaped microchannel antisolvent precipitation combined with spray-drying. The effects of the key operation parameters, including (1) silybin concentration, (2) solvent flow rate, (3) antisolvent flow rate, and (4) overall flow rate, were investigated on the particle size and size distribution. The experimental results indicated that the average particle size decreased from 101 nm to 26 nm with the reduction in the flow rate of silybin solution from 40 to 2 mL/min. However, with increasing overall flow rate at a fixed flow ratio of five, the average particle size decreased from 62 nm (at 6 mL/min) to 39 nm (at 18 mL/min), and then increased to 77 nm (at 96 mL/min). Moreover, the average particle size initially decreased, and then increased, with increasing silybin concentration and antisolvent flow rate. The as-prepared silybin nanodispersion with an average particle size of 26 nm exhibited a faster dissolution rate of 10 times than that of raw drug. This work showed that the continuous preparation in a T-shaped microchannel was a simple and economic way to prepare water-insoluble drug nanodispersion with tunable sizes. (C) 2013 Elsevier B.V. All rights reserved.