Hollow needles of micron dimensions have previously been fabricated and envisioned for use with transdermal patches or infusion pumps to achieve painless delivery of drugs to the skin for local and systemic effects without the need for hypodermic needles. However, little work has been carried out to identify methods to effectively use hollow microneedles for drug delivery. To address this need, we inserted hollow, glass microneedles into hairless rat skin in vivo and human cadaver skin in vitro and then imaged infusion of dye molecules, insulin, polymer microparticles, and cells into the skin by brightfield and fluorescence microscopy. The depth of needle penetration into skin was controlled by inserting needles with a rotary drilling device, which enabled localized injection within the epidermis or dermis with +/-60 microm resolution. Although small quantities of fluid could be injected after needle insertion into skin, partial retraction of the needle by withdrawing back 100-300 microm or vibrating the microneedle array dramatically increased infusion flow rate. We conclude that hollow microneedles can be used for precise microinjection into skin, especially when a single needle is inserted by rotary drilling and then retracted part way before infusion or a microneedle array is inserted by mechanical vibration.