One of the most notable and initial indications of the body's response to an implanted material is the inflammatory response, a process which is known to be largely influenced by the activation of macrophages and other cell types. Thus, the magnitude of the inflammatory response can be related to the level of activation of macrophages. As certain well defined morphological changes are known to accompany cell activation, we quantitatively evaluated the cell--substrate interactions, between a range of polymeric materials and isolated macrophages in vitro, using microscopy and image analysis. This enabled us to assess the morphology of the cells, and how the morphology of the macrophages was influenced by changes in time and substrate. This method provided detailed images which were used to evaluate cell-substrate interactions. It was found that, polyurethane (PU) and poly(dimethylsiloxane) (Si) samples displayed a similar pattern in cell behaviour, whilst macrophages placed in contact with polyvinylchloride (PVC) samples continually displayed a more activated morphology with increasing time throughout the test period. As well as providing a detailed analysis of cell-substrate interactions this study also highlighted the advantages of employing an image analysis program for a more comprehensive and reproducible form of assessment of cellular morphology.