BACKGROUND: Several aerosol production systems have been used for aerosol insulin production. However; since the first studies several new models of jet-nebulizers and ultrasound nebulizers have been introduced in the market.MATERIALS AND METHODS: Three different models of jet-nebulizers (different brands, same properties) and three different ultrasound nebulizers (different brands, same properties). Six residual cups (2 small ≤ 6 ml and 3 large ≤ 8 ml) were used for the jet-nebulizers. The ultrasound nebulizers were used with their facemasks or with their inlets which were included in the purchase package.RESULTS: Ultrasound nebulizers; LANTUS produces by far the lowest mean droplets (2.44) half the size of the other two drugs (4.43=4.97). GIMA nebulizer is the most efficient producing one third of the droplet size of SHIMED and one second of EASYNEB (2.06<3.15<6.62). Finally, the 4 ml loading concentration is more suitable for supporting the production of smaller droplets (3.65<4.24). Drugs and nebulizers act interactively yielding very large droplets when ACTRAPID and HUMULIN are administered in joint with SHIMED nebulizer (9.59=7.72). Jet-nebulizers; HUMULIN again is the least preferred insulin since it hardly reaches the low but equal performance of others at the loading level of 6 ml. Residual cups E and B produce uniquely lower mean droplets at loading level 6.CONCLUSIONS: Ultrasound nebulizers; the best suggested combination should be LANTUS insulin, GIMA nebulizer administered at loading dose of 4 ml jet-nebulizers. A global review can give the best combination: the lowest mean droplets are produced when the drugs LANTUS (mostly) and ACTRAPID are administered, applying the SUNMIST nebulizer in concert with residual cup B at loading levels of 6 ml.