Macrophages (mphi) play a crucial role in the immune system. The rat offers unique advantages for studying the biology of mphi. Firstly, monoclonal antibodies (mAb) against many rat mphi surface glycoproteins have become available. These have not only demonstrated a considerable heterogeneity among mphi, but have also allowed the characterization of various mphi surface molecules in terms of structure, expression regulation and function. Furthermore, substantial numbers of rat mphi can be isolated from various sites (e.g. blood, peritoneal cavity, lung and other tissues), enabling proper molecular and functional analysis of these mphi populations. Finally, a number of (unique) experimental models for human diseases have been developed in the rat, making possible the evaluation of the involvement of mphi in pathogenesis. For this, a method for the selective elimination of mphi from various tissues in vivo has proven very useful. Here, we will review the contribution that the rat has made to understanding the immunobiology of mphi. In particular, we will discuss the surface (glyco)proteins on rat mphi in differentiation and function, and the involvement of mphi in rat models of disease.