The repeated activation of a microelectromechanical systems (MEMS) drug delivery device was studied in vivo in rats to examine the effect of implantation on the device operation and the effect of electrochemical activation on the inflammatory and wound-healing response. The MEMS devices were fabricated from a silicon wafer into which reservoirs were etched and covered with gold membranes. The membranes were electrochemically removed when an anodic voltage was applied. Devices were implanted subcutaneously both with and without stainless steel mesh cages for 4, 7, 14, 21, or 28 days before activation. Devices were activated every other day for five activations. Leukocyte concentrations indicated that both the application of voltage and the gold corrosion products elevated the inflammatory response which was resolved within 48 h after each activation. The efficiency of gold membrane removal was not impaired throughout the implantation, although a bimodal distribution of background current densities was observed after long implantation times. The thickness of the fibrous capsule surrounding the MEMS devices was similar between activated and control devices explanted at each time point. It was concluded that the repeated activation of MEMS drug delivery devices was successful and the activation produced an acceptable biological response that resolved promptly.