A CAD/CAM system has been developed for rapid prototyping (RP) of microfluidic devices based on excimer laser micromachining. The system comprises of two complementary softwares. One, the CAM tool, creates part programs from CAD models. The other, the Simulator Tool, uses a part program to generate the laser tool path and the 2D and 3D graphical representation of the machined microstructure. The CAM tool’s algorithms use the 3D geometry of a microstructure, defined as an STL file exported from a CAD system, and process parameters (laser fluence, pulse repetition frequency, number of shots per area, wall angle), to automatically generate Numerical Control (NC) part programs for the machine controller. The performance of the system has been verified and demonstrated by machining a particle transportation device. The CAM tool simplifies part programming and replaces the tedious trial-and-error approach to creating programs. The simulator tool accepts manual or computer generated part programs, and displays the tool path and the machined structure. This enables error checking and editing of the program before machining, and development of programs for complex microstructures. Combined, the tools provide a user-friendly CAD/CAM system environment for rapid prototyping of microfluidic devices.