Purpose: To compare the matrix metalloproteinase-8 (MMP-8) levels in the peri-miniscrew implant crevicular fluid (PMCF) of immediate-loaded and delayed-loaded miniscrew implants at different time intervals. Materials and Methods: Titanium orthodontic miniscrews were placed bilaterally in the attached gingiva of 15 patients between the maxillary second premolar and maxillary first molar for en masse retraction. This split-mouth study was designed to have an immediate-loaded miniscrew on one side and a delayed-loaded miniscrew on the other side that was loaded 8 days after miniscrew placement. PMCF was collected from the mesiobuccal aspects of the immediate-loaded implants at 24 hours, 8 days, and 28 days after loading, and from the delayed-loaded miniscrew implants at 24 hours and 8 days before loading and 24 hours and 28 days after loading. An enzyme-linked immunosorbent assay kit was used to assess MMP-8 levels in the PMCF samples. Unpaired t test, ANOVA F-test, and Tukey post hoc test were used to evaluate data at the P < .05 level. Results: Although there were slight alterations in the MMP-8 levels in the PMCF over time, there was no statistically significant difference in the MMP-8 levels between groups. There was a statistically significant decrease in the levels of MMP-8 between 24 hours after miniscrew placement and 28 days after loading on the delayed-loaded side (P < .05). Conclusion: The MMP-8 levels did not vary much between immediate-loaded and delayed-loaded miniscrew implants as a result of the force application. However, there was no significant difference between immediate loading and delayed loading in terms of biologic response to mechanical stress. The increase in MMP-8 levels after 24 hours post-miniscrew insertion, as well as the subsequent gradual reduction over the course of the study period in both immediate and delayed groups after loading, is probably due to the bone adapting to stimuli.