Previous investigations on mammalian cells have shown that real microgravity in space and/or simulated microgravity causes severe cellular modifications. Aim of the study was to use Digital Holographic Microscopy (DHM) to investigate morphological changes of cells under simulated microgravity generated by the Random Positioning Machine (RPM) in real-time. Preliminary studies were carried out on mouse myoblasts (C2C12). Besides showing cellular modification under simulated microgravity similar to the results obtained by using conventional methods, an increase of the phase height of the cell was measured which have not been reported yet. Our technique provides a new approach in the study of cellular adaptations to microgravity, providing real-time images of living cells.