Suture compression is a widely used approach to inhibit maxillary growth; however, biological responses in sutures to compressive force are still unclear. The objective of this pilot study was to investigate the matrix metalloproteinase (MMP) expression and osteoclast activities during the midpalatal suture compression.56 six-week old male C57BL/6 mice were randomly assigned to the control and compression groups. The mice in the compression and control groups received helix springs bonded to the maxillary molars delivering initial compressive forces of 0.20 and 0N (no activation), respectively. On Days 1, 4, 7 and 14, animals were sacrificed and scanned using micro-computed tomography to quantify suture width and bone mineral density. Serial histological sections were stained with HE, TRAP, and immunohistochemistry to observe changes in bone resorption, osteoclast activities, and MMP-1, 8, and 13 expressions. Bone volume/total volume (Bv/Tv) ratio, osteoclast count, osteoclast covering area, and MMP expression intensity were measured. The Mann-Whitney and the Kruskal-Wallis tests with Bonferroni post-hoc corrections were performed to compare differences between groups and between time points in the same group at significant level of P0.05.Compared to the control, suture width in the compression group was significantly reduced on Day 1, but continuously widened with reduced bone mineral density afterwards. With MMP-1 and -13 evidently intensified expressions, osteoclast number and activities significantly increased, leading to reduced Bv/Tv ratio and progressive bone resorption from Days 4 to 14.Suture compression elevated the MMP-1 and 13 expressions, activated osteoclasts, reduced bone density, and induced bone resorption adjacent to the suture. It suggests that suture compression can be used for bone volume reduction.