Fluorinated polyimide waveguides were fabricated by CO2 laser direct-writing. The poly(amic acid) micro-region irradiated by CO2 laser beam was studied with FT-IR micro-spectroscopy. The FT-IR spectra implied that the laser induced thermal-imidized polyimide was of optical anisotropy, and the imidization degree of exposed micro-region increased with the rising of output laser power. The increased aspect ratio of waveguide and smoothness of surface can be achieved by increasing the pre-cured temperature (below 120°C) and writing speed, and optimizing laser power and the distance between the lens and the annular aperture. The guided light was clearly confined to the core of the fabricated waveguide, which means this technique can be used for fluorinated polyimide waveguide fabrication.