Macrophages play a critical role in regulating immune reactions induced by implanted biomaterials. They are highly plastic and in response to diverse stimuli in the microenvironment can exhibit a spectrum of phenotypes and functions. In addition to biochemical signals, the physical properties of biomaterials are becoming increasingly appreciated for their significant impact on macrophage behaviour, and the underlying mechanisms deserve more in-depth investigations. This review first summarises the effects of key physical cues - including stiffness, topography, physical confinement and applied force - on macrophage behaviour. Then, it reviews the current knowledge of cellular sensing and transduction of physical cues into intracellular signals. Finally, it discusses the major challenges in understanding mechanical regulation that could provide insights for biomaterial design.