We hypothesized that a 10-s rest interval (at zero load) inserted between each load cycle would increase the osteogenic effects of mechanical loading near previously identified thresholds for strain magnitude and cycle numbers. We tested our hypothesis by subjecting the right tibiae of female C57BL/6J mice (16 wk, n = 70) to exogenous mechanical loading within a peri-threshold physiological range of strain magnitudes and load cycle numbers using a non-invasive murine tibia loading device. Bone responses to mechanical loading were determined via dynamic histomorphometry. More specifically, we contrasted bone formation induced by cyclic versus rest-inserted loading (10 s rest at zero load inserted between each load cycle) by first varying peak strains (1000 µ, 1250 µ, or 1600 µ) at fixed cycle numbers (50 cycles/d, 3 days/wk for 3 wk) and then varying cycle numbers (10, 50, or 250 cycles/d) at a fixed strain magnitude (1250 µ). Within the range of strain magnitudes tested, the slope of periosteal bone formation rate (p.BFR/BS) with increasing strain magnitudes was significantly increased by rest-inserted compared to cyclical loading. Within the range of load cycles tested, the slope of p.BFR/BS with increasing load cycles of rest-inserted loading was also significantly increased by rest-inserted compared to cyclical loading. In sum, the data of this study indicate that inserting a 10 s rest-interval between each load cycle amplifies bone's response to mechanical loading, even within a peri-threshold range of strain magnitudes and cycle numbers.