In this paper, the authors present a constant voltage constant current readout circuit for Ion-Sensitive Field-Effect Transistor (ISFET). The study and investigation of ISFET performance using linear technology simulation program with integrated circuit emphasis LTSpice in order to identify the characteristics relationship of an ISFET variable is included. A macro-model of an ISFET had been created and tested using simulation program, in order to make sure the performance results of ISFET as the ion concentration (pH) changes, the current of the transistor will change accordingly.