Objective: The purpose of this study was to determine the effect of type I collagen on the expression of osteopontin (OPN) induced by insulin-like growth factor (IGF)-1 in human periodontal ligament (HPDL) cell, since extracellular matrices have been shown to influence cell behavior and modulate cellular response of cell to growth factor. Methods: Human periodontal ligament cells were obtained from periodontal tissue and maintained in DMEM containing 10% fetal bovine serum. The cells were seeded on plastic or collagen coated plate in the presence or absence of 5 ng/ml of IGF-1. After 60 hours, the expression of OPN was analyzed by reverse transcription-polymerase chain reaction. Result: The results showed no significantly changes of OPN expression in HPDL cells when cultured on collagen-coated plate as compared with the control. Addition of IGF-1 could induce the expression of OPN in HPDL cells cultured on the plastic. Interestingly, the enhanced effect of IGF-1 on the expression of OPN was observed when HPDL cells were grown on collagen-coated plated. Conclusion: The response of HPDL cells to IGF-1 could be modulated by type I collagen. The increase level of OPN may reflect the function of tissue remodeling since OPN is an extracellular matrix protein involved in the inflammatory process and tissue repair. This result suggests the interaction between IGF receptor and the signal from extracellular matrix, especially type I collagen, in the regulation of the expression of osteopontin.