The comprehensive application and potential danger of high temperature autoclave was discussed. The influence of thermal stress of autoclave in the reaction process of prepare biodiesel was studied. Utilizing simulation software, visualization of the structure and security was finished and thermal stress mould of ANSYS was employed to analyze the thermal stress distribution and deformation of autoclave. After the 3D (3 dimension) autoclave body model was created by AutoCAD, ANSYS Multiphysics was used to simulate the change of thermal stress of autoclave. Taking direct method for example, the whole simulation process was introduced. Validating by some equipment necessarily, the results of analysis are credible.