Objective: To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Materials and Methods: Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Results: Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed b-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time-and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed b-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Conclusions: Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation. (Angle Orthod. 2017;87:193-199)