Abstract: AIM: 2-(3-Estrone-N-ethyl-piperazine-methyl) tetracycline(XW630) is a novel bone-targeted estrogen which shows stronger action in enhancing bone formation than estrone on ovaritectomized rats while shows weaker estrogen-like activity on mouse uterus. Therefore, it may be a potential compound for prevention and treatment of postmenopausal osteoporosis. The effects of XW630 on the levels of c-fos and c-jun mRNAs and their product proteins in long bone were studied for insight into the mechanism by which XW630 acts on bone. METHODS: The long bones of fetal mice of 16 days old were cultured in BGJb medium and treated with 10^-7 mol.L^-1 XW630 or 10^-7 mol.L^-1 estrone. After cultured for 48 h, the levels of mRNAs of c-fos and c-jun were determined by approach of in situ hybridization. Immunohistochemical analysis of c-fos protein and c-jun protein were also performed. RESULTS: The levels of c-fos mRNA, c-jun mRNA and their proteins in resting zone, proliferative zone and hypertrophic zone were all upregulated. XW630 showed stronger effects on epiphyseal plate than estrone. CONCLUSION: The results suggest the possibility that XW630 enhanced endochondral bone development by upregulating the expression of c-fos and c-jun in epiphyseal plate. Their proteins may in turn rapidly regulate expressions of other genes that relate to bone growth and in which there are AP-1 sites.