Biodiesel is an alternative fuel for diesel engines which is defined as a fuel comprised of mono alkyl ester of long chain fatty acids produced by chemically reacting a vegetable oil or animal fat with an alcohol such as methanol. It is a non-toxic, biodegradable, relatively less inflammable fuel compared to the normal diesel. Biodiesel is also essentially free of sulfur and aromatics that produces lower exhaust emissions than normal diesel. Because of high cost of edible vegetable oils such as canola, soybean, and corn, it seems that commercialization of biodiesel production from edible vegetable oil is not economically favorable, while using waste vegetable oil as the feedstock, which is much less expensive than edible vegetable oil, can reduce the costs of biodiesel production. In addition, the conversion of waste vegetable oil into fuel also eliminates the environmental impacts caused by the harmful disposal of these waste oils. Transesterification or alcoholysis is the reaction of a fat or oil with an alcohol to form biodiesel and glycerol. Transesterification reaction can be performed with alkali, acid or enzyme catalyst. The homogeneous alkaline and acidic catalyst processes have complex and energy-consuming separation and purification steps. Supercritical methanol is a method of transesterification reaction without the presence of catalyst in the process. The absence of catalyst in the process, leads to simpler separation and purification steps of biodiesel. The addition of co-solvents, such as carbon dioxide, propane and hexane can decrease the operating temperature, pressure and the amount of alcohol. The Response Surface Methodology was applied to analyze the effect of four independent variables (molar ratio of methanol to oil, reaction temperature, pressure and time) on the yield of the biodiesel production in supercritical methanol method. CO 2 was used as a co-solvent and pressure enhancer, simultaneously. Waste vegetable oil was used as raw material and transesterification reaction was performed in a supercritical batch reactor. The central composite rotatable design was used to maximize the yield of the biodiesel. The optimal values of variables were determined by RSM and genetic algorithm to be 33.8:1 (methanol/oil molar ratio) 271.1°C, 23.1 MPa and 20.4 min reaction time for the maximum predicted yield of 95.27% (g/g). The Response surface analysis showed that the data were adequately fitted to second-order polynomial model (R 2 =98.6%). The all linear and quadratics terms, as well as the interaction between molar ratio-time and temperature-time, had significant effects on the biodiesel yield. Molar ratio of methanol to oil from 10 to around 34 had a positive effect on the yield, but beyond 34 had a negative effect. The yield of the biodiesel was increased with higher temperature up to around 271°C, but in upper temperatures beyond 271°C a gradually reduction was occurred in the biodiesel yield.CO 2 pressurehad a positive effect on the yield, but for the pressures up to around 23 MPa, a gradually reduction in biodiesel yield was observed. Biodiesel yield was increased in longer reaction times due to the extent of transesterification reaction progress. Moreover, an irreversible first order kinetic model was successfully correlated to the experimental transesterification data with 3.37 (s -1 ) and 31.71 (kJ/mol) as the frequency factor and activation energy of the process. Key Words: Biodiesel, transesterification, supercritical methanol, waste vegetable oil, optimization, response surface methodology.