Backgrounds: Osteoporosis is a common aging-related degenerative bone disease, particularly in postmenopausal women, that have a reduced estrogen level due to aging. Various factors have been recognized to promote osteoporosis development, such as microRNAs (miRNAs), which regulate the balance between osteogenesis and osteoclasis. Aim: This study was to profile miRNAs in the ovariectomy osteoporosis mice with miRNA profiling array, and to associate the deregulated miRNAs with osteogenesis. Materials and Methods: The authors firstly profiled, with miRNAs microarray analysis, the serum miRNAs in a mouse model with postmenopausal osteoporosis, post-ovary excision. Then they validated the dysregulated miRNAs via quantitative real-time polymerase chain reaction (qRT-PCR) method. In addition, these deregulated miRNAs were subjected to a pathway analysis. Results: It was indicated by the present results that in the ovariectomized mice, ten miRNAs were upregulated, such as miR-27a-5p, miR-26a-5p, miR-106a-5p, and miR- 133a-5p and the upregulation of miR-26a-5p, miR-133a-1-5, miR-141-5p, miR-200a-5p, and miR-205-5p were validated by the followed qRT-PCR method. In addition, the pathway analysis demonstrated that these miRNAs might inhibit the bone formation via regulating osteogenesis. Conclusions: In conclusion, the authors found the upregulation of miRNAs, which downregulates osteogenesis in a mice model of postmenopausal osteoporosis. The present findings suggest the potential inhibition by miRNAs in osteogenesis in postmenopausal osteoporosis.