Delivery of poorly water-soluble compounds by use of nanosized lipid carriers has attracted much attention in pharmaceutical and therapeutic areas in recent years. However, it is difficult to formulate poorly water-soluble compound loaded lipid nanoparticles with narrow size distributions and proper drug load properties. In the present work, we introduce a precise mechanical manufacture method, the microcutting approach, to fabricate a microchannel system on a stainless steel slab, which was then assembled and employed to prepare poorly water-soluble drug loaded solid lipid nanoparticles (SLNs) by liquid flow-focusing and gas displacing techniques. A poorly water-soluble drug, puerarin, was used as the model drug, and the production of puerarin-loaded SLNs was achieved under various conditions. Particle size distribution of the obtained drug-loaded SLNs was measured by dynamic light scattering (DLS), and the particle morphology was observed by transmission electron microscopy (TEM). The state of the drug-loaded SLNs was analyzed by differential scanning calorimetry (DSC), and the drug load was determined by high-performance liquid chromatography (HPLC). The results showed that microchannels fabricated by the present mechanical microcutting method were excellent in surface quality and precise in channel sizes and shapes, which are easily scaled-up. The puerarin-loaded SLNs prepared by the present microchannel system have a narrow size distribution and the mean particle size varied with the velocities of fluids and the lipid concentration. The drug load capacity of puerarin was influenced by preparation parameters, like the flow velocities of liquids and the concentrations of lipid and puerarin. Therefore, by employing suitable preparation parameters, one can produce poorly water-soluble drug loaded SLNs with expected sizes and drug load capacities by use of microchannels fabricated by the microcutting method, which could be an effective and alternative approach for scale-up production of those new nanosized delivery systems containing poorly water-soluble drugs for potential pharmaceutical and therapeutic applications.