We used polychrome sequential labeling to study the dynamics of subchondral bone sclerosis during developing arthrosis in knee joints of male STR/1N mice. This technique, using four different colored vital markers, gives detailed information about the site and time of new bone formation in the subchondral bone. In arthrotic joints, we found fluorescent bands arranged excentrically around the marrow cavities always pointing towards the cartilage lesions. The linear separation between the first label and the anatomic surface of the bone marrow cavity varied considerably between the experimental groups. In arthrotic joints, we found bone growth rates 3–4 times greater than in control joints. We also found that the degenerative process in cartilage and subchondral bone was a local phenomenon, because in areas with normal cartilage next to the sclerotic lesions appositional bone growth rates were unaffected.