A method is proposed for rapid prototyping of Poly (methyl methacrylate) (PMMA) microfluidic devices utilizing a micromilling machine. The present study is to investigates the influence of micromilling machining parameters which include spindle speed, feed rate, and depth of cut on the surface roughness of the machined polymer microfluidic devices. The devices have been machined on a PMMA substrate using 200 µm diameter endmill tool (Titanium Aluminum Nitride (TiAIN) coated solid carbide material). Surface roughness is considered an important parameter for influencing fluid flow at the microscale. The surface roughness has been measured using Infinite Focus Microscopy (IFM) tool. Taguchi’s method is used for designing the experiments and optimization of machining parameters. The results showed that a surface roughness of 67.3 nm has been achieved using machining parameters including spindle speed of 4000 rpm, feed rate of 10 mm/min and the depth of cut of 10 μm. Taguchi’s factor analysis on the samples showed that the depth of cut has the largest impact on the average surface roughness