Objective To develop a method for measuring the piezoelectric effect in wet bone. Methods A piezoelectric voltage measurement system of wet bone was designed, which employed platinum/iridium electrodes to detect the piezo-voltages and an ultra-high input impedance bio-amplifier to amplify the piezo-voltage signals, respectively. Because there was nearly no electric current in the buffer solution, even the electrodes that did not contact the bone sample could detect the piezoelectric voltages at the side of two bone samples. Results Voltage-time curves were obtained under the trapezoidal loading, and the results were confirmed to be piezoelectric voltages produced from bone by experiment. A total of 6 samples were tested. The measurement results showed that the piezo-voltages of wet bone were induced during the dynamic loading process, which was consistent with dry bone. Conclusions Measurement of the piezo-voltages in wet bone was developed by employing platinum/iridium electrodes for detecting the piezo-voltages and an ultra-high input impedance bio-amplifier for amplifying the piezo-voltage signals, and the validity of the test system was confirmed via experiments. The peak value of piezo-voltage was between -0.75 mV and -1.69 mV under the loading peak value 9 N. The results are helpful to investigate the relationship between bone growth and electric signals, which provides the theoretical references for researches on bone healing in clinic.