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Unloading, such as denervation, resulted in bone loss. The aim of this study is to evaluate effects of minimally invasive laser therapy system (MILTS) for treatment of bone loss during unloading. Nineteen 6-week-old ICR female mice (approximate weight 24 g) were used. Twelve mice served as sciatic neurectomy (denervation group, DENER) for right hind limb and seven mice served as control (wild type group, WT). Six mice were directly irradiated laser (wavelength: 660 nm, optical power: 10 mW, energy density: 3J) on bone by using minimal invasive laser probe in DENER group for 2weeks. The other six mice in DENER group served as sham treatment (sham group, SHAM). The mice were scanned at 0 week, before denervation, after 2weeks and after 4weeks by using in vivo micro-CT. Structural parameters and volume bone mineral density (vBMD, g/cm3) in the trabecular bone were measured. The vBMD(11%,p < 0.01), BV/TV (57%,p < 0.01), Tb.Th (23%,p < 0.05) and Tb.N (57%,p < 0.01) were significantly bigger and the Tb.Sp (42%,p < 0.05), SMI (62%,p < 0.05) and Tb.Pf (41%,p < 0.01) were significantly smaller in LASER group compared with SHAM group after 2weeks irradiation of laser. These results showed that the MILTS might keep bone quantity as well as quality during unloading. Therefore, the MILTS might be used for treatment of bone loss during unloading.