The goal of this study was to verify that a fully implanted microelectrode with modulated surface may have a reduced rising rate of total impedance and a longer life time. In the previous work, alkanethiolate self-assembled monolayers (SAMs) surface as protein-resistant spacer or cell-repulsive dense-packed spacer has been verified from in vitro experiments. In this study, microelectrodes with the same surface modulation were implanted into the subcutaneous layers of Wistar rats. Nine rats were implanted with the microelectrodes and the total impedance data were measured every 24 h for 2 weeks after implantation. An equivalent electrical circuit model of the electrode-tissue interface was established and parameters were estimated by using an optimization algorithm. Four out of nine rats had manifested acute inflammation reaction and the rests revealed only slight tissue response. Histological examination for the inflammatory group showed fibroblasts, macrophages, and polymorphonuclear leukocytes in adjacent to the electrode contact surface. In the inflammatory group, no significantly difference in total impedance was found in both types of electrodes. However, the trend of total impedance of SAMs-treated electrodes could maintain a steady state value after 1 week. For the non-inflammatory group, both types of electrodes could reduce the impedance value within implanted days. The tissue resistance might be related to the thickness of cells adhered upon the electrode contacts.