High molecular weight water-soluble chitosan(WSC), having an average molecular weight of 300,000 Da and a degree of deacethylation over 90%, can be produced using a simple multi-step membrane separation process. In this study, the trabecular bone area and thickness in ovariectomized(OVX) rats decreased by almost 50% from those in sham-operated rats. WSC was evaluated for inhibition of the progress of bone loss induced by OVX rats. We measured bone histomorphometry in sham, OVX or WSC-administered OVX rats. From light microscopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in OVX rats, whereas those of the same bone in sham-operated rats were composed of fine particles. The trabecular bone area and trabecular thickness in OVX rats decreased by 50% from those in sham rats, these decreases were completely inhibited by administration of WSC at a concentration of 15 mg/kg/daily for 7 weeks. In this study, the mechanical strength in femur neck was significantly enhanced by the treatment of WSC for 7 weeks. In OVX rats, free T(3) was normal in all cases, whereas free T(4) was significantly increased. Although there was no difference between OVX and WSC-administered rats in T(3) level, we have found significant difference between them in T(4) level. These results strongly suggest that WSC is effective in preventing the development of bone loss induced by OVX in rats.