Abstract: The development of a 16-channel electrophysiological signal detecting system based on the microelectrode array is described. The detecting system consists of hardware and software components, and the hardware can be divided into the following three modules: Microelectrode array interface module, which is used for connection of the micro-electrode array and the detecting system; Multi-channel signal amplification module, which is used for signal amplification; Data acquisition module, which is used for high speed data acquisition. The software design uses multi-threaded and multi-caching technology to ensure the datas real-time observation and analysis. The main parameters of the detecting system are tested, and the laboratory-made microelectrode array is used for the detection of acute hippocampus slices. The system,s input noise Vrms is less than 2 V, total gain of the amplifier is 1000, frequency band is 10-3000 Hz. The neural electrophysiological signals of brain slice are successfully detected. With the proper design of hardware and software system, the voltage revolution of system can attain 0.6 V which can meet the demand of neural electrophysiological signal detection.