The present research work is a novel cost-effective method for synthesis of magnetite. Magnetite is a carrier which is used in the targeted drug delivery system. The conventional methods of preparation of magnetite take around 6-7h for the completion of reaction; moreover, the particle size of magnetite which we get by the conventional methods is above 5 mu m, so the present work aims at preparing magnetite with microwave assistance which has found to reduce reaction time with particle size obtained below 5 mu m. The aim of this study was to optimize magnetite synthesis using 2(3) factorial design by Design-Expert software. Magnetites were synthesized using oxidation of ferrous sulfate. In the next step, the effects of different variables on particle size are studied, including the stirring speed, microwave power (W), and stirring time. Based on the type and the variables studied, eight formulations were designed using factorial design method, and were then prepared, and their particle size was determined. Finally, selected magnetite syntheses were evaluated from the viewpoints of scanning electron microscopy (SEM) and x-ray diffraction (XRD). Results revealed that magnetite obtained from the solutions generated Design-Expert software could be selected as the best and optimized formulations due to their lowest particle size.