This paper deals with the subject of "in situ" development of environmental-transmission electron microscope (E-TEM) holder assemblies. In E-TEM, the sample is continuously subjected to gases as opposed to conventional TEM where the sample is under high vacuum. E-TEM offers the possibility of achieving a new level of material analysis. E-TEM allows obtaining information about chemical information during the reaction at atomic level. Rarefied gas dynamics analysis is used to assess the proposed design. The analysis is focused on determining the molecular distribution inside the vacuum chamber and calculating the impingement rate on the target surface of the specimen. Simulations are performed to predict the molecular interaction with the specimen at given pressures to determine the proper position of a specimen within a vacuum chamber to optimize and predict reaction characteristics. Results of direct simulation Monte Carlo show that the two sides of the sample operate at different temperatures due to the gas flow and experience different molecular distributions.