BACKGROUND: Gene expression analysis is useful for assessing cellular behavior and may improve our understanding of the initial cellular response to mechanical load leading to tendon degeneration. This study assessed gene expression of MMP-1 and MMP-3, genes associated with matrix degradation, in tendons exposed to cyclic loads within physiologic range. METHODS: Six flexor tendons from each of ten New Zealand White rabbits were harvested and randomly assigned to one of the following six groups: load deprived for 18h; cyclically loaded for 18h to a peak stress of 2MPa; 3MPa; 4MPa; 5MPa; or snap frozen in liquid nitrogen. MMP-1, MMP-3 and 18s mRNA expression was measured by qRT-PCR. FINDINGS: No significant differences in MMP-1 mRNA expression levels were found between loading groups. MMP-3 expression was significantly inhibited (57%) in tendons cyclically loaded to a peak stress of 4MPa in comparison to load deprived tendons, however, when peak stress was increased to 5MPa, expression was no longer significantly lower compared to stress shielded tendons. INTERPRETATION: The results suggest a 'U' shape relationship between load and MMP-3 expression. The lack of change in MMP-1 expression with loading was unexpected as inhibition of MMP-1 in response to mechanical load has been demonstrated in previous studies. In conclusion, we demonstrate that MMP-3 expression is modulated by cyclic load and is sensitive to load magnitude. MMP-1 mRNA expression is not significantly modulated by cyclic load in this model.