Grouper is one of the major economic fish in Taiwan. Recently, the grouper farming production is restricted due to the long duration of culturing a fish to size for sale. Therefore, it is important to develop grouper with higher growth rate. Leptin is a kind of hormone, which is also a suppressor of orexigenic gene . Disruption of leptin signaling significantly improve weight-gaining ability of mouse. In this study, we will use immune-inhibition technique to establish leptin-inhibited grouper by oral delivery system. W e noticed the PEIa-gL6E level achieved induction limitation with 0.1mM IP TG. After purification, we determine the dosage of target protein in oral inhibitor. I n animal test, the fish were fed by three different concentrations of oral inhibitor, and the body weight, length, and food intake were recoreded. The weight of grouper gained 7-11% with the oral inhibitors feeding, while the length only showed slight changes (<3%). Besides, the food conversion ratio of group fed with oral inhibitors were higher than control. I n conclusion, leptin may affect the accumulation of body weight instead of body length. T his provides us insights to investigate the orexigenic and anorexic responds that leptin involved in.