Fabrication of biodegradable polylacticcoglycolic acid (PLGA) microneedle array through CO2 laser processing have been studied and analyzed. The high-Aspect-ratio microneedle mold can be obtained using the rapid and low-cost laser processing compared to conventional photolithography and dry etching processes. The laser processing on PDMS results in the problems of scorches and re-solidification. Here, we use the direct-write laser processing microneedle mold structure on PMMA and then perform two-casting PDMS process to form female microneedle mold. Then pour PLGA into PDMS female mold pre-treated by O2 plasma and drying in vacuum chamber. Finally, the complete PLGA microneedle array is released from the PDMS mold which is reusable. The polymer microneedle depth can be from hundreds of micrometers to millimeter that is related to the PMMA structure profile and determined by CO2 laser power and scanning speed. The modified integration of laser processing and molding process is maskless, simple, and low-cost for rapid prototyping.