The development of chronically implanted electrodes attracts much attention since these electrodes are much favorable for monitoring changes of neurotransmitters in brain science. The research in this field focused mainly on chemical modification to improve the potential stability and less on the biocompatibility. In this work, for the first time, we proposed the concept of cell-membrane electrodes based on a basic hypothesis using animal's self-cell membrane to reduce animal exclusiveness (hyperacute rejection and chronic rejection). As a proof of concept, we first studied cell-membrane reference electrodes for chronically implanted electrodes. Red cell membrane (RCM) was extracted from rat blood and coated on the chemically modified Ag/AgCl electrodes. It was found that ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium hexafluorophosphate (BDMI) showed good performance rather than Nafion used as coating film for protection of silver chloride on Ag wire and support of the cell membrane. Electrochemical impedance spectra supported that charge-transfer resistance nearly kept constant before and after the electrodes were implanted into the rat's brain tissues for 28 days. Immunohistochemical analysis of the implant sites in the rat's brain tissues indicated that the extent of glial scarring arising from the Ag/AgCl/BDMI/RCM electrodes was smaller than that of both Ag/AgCl/Nafion and Ag/AgCl/Nafion/RCM electrodes after 28 days of implantation. The RCM-coated Ag/AgCl/IL electrodes showed a relatively potential stability compared to RCM-noncoated Ag/AgCl/IL electrodes after 28 days of implantation. Additionally, the current-voltage curve demonstrated that the RCM-coated electrodes can be used as polarized electrodes. This work demonstrated that the RCM, which was coated on the Ag/AgCl/IL electrodes, can significantly improve the biocompatibility and potential stability of the RCM-noncoated Ag/AgCl/IL electrodes implanted in the rat brain. The cell-membrane-coated electrodes will serve as a lighthouse in guiding the design of chronically implanted electrodes for in vivo electrochemical detection.