The objective of this research is to optimize of biodiesel production with ultrasound assisted. Optimization was used central composite design methods. Biodiesel was produced from frying oil with KOH catalyst and ultrasonic assisted. The variables were investigated temperature, catalyst concentration and ratio of methanol to oil. Biodiesel was separated from reactant and impurities with decantation process and distillation process. The results of research obtained optimum conversion 85.95% in operation condition are methanol/oil 5.05:1, catalyst concentration 1.65% and temperature reaction 50°C. Mathematic modeling for describe in this process like expressed; Y = 86.2107 -7.4287X 1 + 1.0661X 2 + 0.6289X 3 -2.5319X 1 2 -2.0603X 2 2 -1.0618X 3 2 .