Reactive granulation and drainage of intra-articularly injected plastic particles in rat knee joints was examined by light and electron microscopy. The knee joints and associated iliac lymph nodes were excised at various intervals after the injection of latex beads (φ1 μm) or fluoresbrite particles (φ0.2 μm or φ10 μm) from 5 min until 3 months after the injection. Particles in the lymphatic or blood vessels were successfully demonstrated by an enzyme-histochemical method (5'-nucleotidase staining). Five min after the injection, most of the particles were scattered on the surface of the synovial membrane, and some particles were phagocytosed by synovial lining cells. After 5 h, neutrophils and had phagocytosed particles which adhered to fibrin in the joint cavity. Twelve h after the injection, after the neutrophils had died, those same particles were phagocytosed by macrophages in the joint cavity. One day after the injection, Fluoresbrite particles (φ0.2 μm) phagocytosed by macrophages were found in the iliac lymph nodes, while latex particles (φ1 μm) were detected in the iliac lymph nodes 3 days after the injection. Some Fluoresbrite particles (φ10 μm) were seen in the 5'-nucleotidase-positive lymphatic vessels in the synovial membrane. Three months after the injection, many macrophages filled with particles had formed granulation tissue in the synovial membrane, and macrophages containing phagocytosed particles were also seen increasingly in the iliac lymph nodes. Our findings suggested that neutrophils and macrophages phagocytosed injected particles in the joint cavity, and that the macrophages brought the particles into the deep layer of the synovial membrane. Phagocytic macrophages also carried the particles to the iliac lymph nodes through lymphatic vessels in the synovial membrane. There were no morphological differences in the processes of granulation and drainage between the two different size plastic particles (φ1 μm and φ0.2 μm), except for the behavior of the macrophages phagocytosing the particles.