We have fabricated and characterized microstructured biodegradable and biocompatible polymer optical fibers using commercially available poly(D,L-lactic acid) (PDLLA). We first report on the preparation of the preforms by means of a novel technique based on transfer molding and on the fiber manufacturing using a regular heat-drawing process. We address the influence of the polymer processing on the decrease of the molar mass of PDLLA following the preform fabrication and the fiber optic drawing process. We investigate the in vitro degradation of the fabricated fibers in phosphate buffered saline (PBS) that reveals 21, 25 and 43% molar mass loss over a period of 105 days for fibers with diameters of 400, 200 and 100 μm, respectively. Cutback measurements return an attenuation coefficient as low as 0.065 dB/cm at 898 nm for a microstructured fiber with a diameter of 219 ± 27 μm. Due to immersion in PBS at 37 °C, the optical loss increases by 0.4 dB/cm at 950 nm after 6 h and by 0.8 dB/cm after 17 h.