Objective To investigate the effect of progranulin (PGRN) on osteoporosis in ovariectomized mice. Methods PGRN-knockout (PGRN-/-) and wild-type mice were ovariectomized to induce postmenopausal osteoporosis models. Next, the bone tissues in all mice were scanned by Micro-CT and three-dimensional reconstruction was performed to detect the micro-structure, followed by trabecula data analysis. The morphology and osteoclasts in the bone tissues of PGRN-/- and wild-type mice were observed by HE staining and TRAP staining, respectively. The expression of receptor activator for nuclear factor-κB ligand (RANKL), tumor necrosis factor α (TNF-α) and P65 were detected by immunohistochemistry. The expression of TRAP mRNA in the mice was measured using fluorescence quantitative PCR and the protein expression of MMP9, MMP14, P65 was detected by Western blot analysis. Results Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) in the PGRN-/- group were significantly higher than those in the wild-type group, while the trabecular separation (Tb.S) in the PGRN-/- group was in the contrary. The degree of osteoporosis was less severe and number of osteoclasts in the PGRN-/- mice were reduced, likewise, RANKL, TNF-α, MMP9, MMP14 and P65 as well as TRAP mRNA were down-regulated in the PGRN-/- group compared with the wild-type group. Conclusion PGRN aggravates the postmenopausal osteoporosis in ovariectomized mice.