AIM　To investigate the effect of particle size and high speed flow of helium gas on the systemic absorption of indomethacin using a needle-less injection system. METHODS　Poly-L-lactic acid microspheres containing indomethacin was prepared by the o/w solvent evaporation technique. After anesthetizing the male hairless rat, microspheres filled in the tube cartridge was accelerated by a stream of helium gas at various velocity in the HeliosTM gun system, and then was introduced to the abdominal skin. RESULTS　Introduction of indomethacin to the hairless rat skin was proportionally increased with enhancing the helium pressure (supersonic flow). Bioavailability and Cmax were also dependent on the helium pressure. CONCLUSION　This method can be used to deliver the powered drug and/or microparticulate systems into the skin tissues and the systemic circulation.