PURPOSE To investigate changes of the cornea induced by lipopolysaccharide (LPS). METHODS Immunohistochemical study using monoclonal antibodies to monocytes, macrophages (ED1, ED2) and MHC class II antigen (OX6) was performed on the corneal wholemounts obtained from normal lewis rats and those after LPS injection. RESULTS Macrophages were noted to be present in whole cornea with a gradually decreased cell density from limbus to central part in normal lewis rats. However, major histocompatibility complex class II antigen (MHC class II)-positive cells were only distributed at limbus. Footpad injection of LPS induced an increase of monocytes and macrophages in whole cornea and a dramatical changes of these cells morphologically. MHC class II-positive cells were only and shortly noted on the surface of the cornea endothelium at early stage after LPS injection. CONCLUSION LPS-induced increase of macrophages in the cornea may be an important defense mechanism in response to LPS challenge. On the other hand, the absence of MHC class II-positive cells both in the normal and in the inflamed cornea may be contributed to the stability of immunological microenvironment within this tissue.