To study the effect of oral administration of icariin (ICA) on periodontitis associated alveolar bone resorption in an osteoporosis mouse model.Three-month old, female C57BL/6J mice were randomly divided into 3 groups: normal group (SHAM), ovariectomy + oral smearing of Porphyromonas gingivalis (Pg) + icariin group (OVX+Pg+ICA), ovariectomy+ Pg group (OVX+Pg). On the second week, the mice underwent ovariectomy to induce osteoporosis. On the fourth week, the mice were treated with Pg by oral smearing for 1 week, 1 time/day. The samples were harvested on the 12th week: the left mandibles were harvested to make the sections and histological staining, to analyze the differences of bone resorption areas among the three groups; the right mandibles were harvested for methylene blue staining, to analyze the differences of bone resorption depth among the three groups. Protein from the periodontal tissues were extracted to analyze the differences of osteoblastic related protein expression level among the three groups. SPSS 16.0 software package was used for statistical analysis.Histological analysis of murine femurs and periodontal tissues demonstrated that the model of periodontitis in osteoporosis mice was successfully created in this study. Quantification of the histological staining showed that compared with OVX+Pg group, icariin treatment decreased the depth of CEJ-ABC and the areas of alveolar bone resorption(P<0.05); Western blot results showed icariin treatment could significantly increase the protein expression level of Runx2, OSX, OCN and OPN in periodontal tissues(P<0.05).Icariin treatment can effectively prevent both bone loss in osteoporosis and alveolar bone resorption induced by periodontitis.