Objective To investigate the effects of different magnitudes of mechanical strain on the expression of MMP-13/TIMP-1 and try to determine the signal transduction pathways in response to mechanical strain in human periodontal ligament cells (HPDLCs) in vitro. MethodHPDLCs were subjected to 0%，6%，12% or 18% elongation for 24 h by using cell stress loading system simultaneously. Then the MMP-13/TIMP-1 mRNA and protein expression in cells were tested by reverse transcription polymerase chain reaction (RT-PCR) and western blotting respectively. Furthermore, specific inhibitors were employed to examine the role of different signal transduction pathway on the expression of straininduced MMP-13 /TIMP-1 in HPDLCs. ResultsThe expression of MMP-13 /TIMP-1 in HPDLCs significantly increased in groups of 6%，12%, 18% elongation in a magnitude-dependent manner compared with the control group (0%) after the mechanical strain treatment for 24 h. PD098059 and cycloheximide could inhibit the increase in MMP-13 and TIMP-1 mRNA expression in response to mechanical strain respectively. Conclusions Different magnitudes of mechanical strain can affect the expression of MMP-13/TIMP-1 in HPDLCs in a magnitudedependent manner, and further affect the periodontium remodeling with the characteristics of degradation and synthesis of extracellular matrix in response to mechanical strain. The ERK-MAPK pathway is involved in straininduced MMP-13 expression while the strain-induced TIMP-1 expression depends on de novo protein synthesis.