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culminating in organ failure and death. Fibrosis, believed to result from a hyperactive tissue repair programme, is characterized by the abnormal presence of the myofibroblast, a specialized type of fibroblast that overexpresses the highly contractile protein a-smooth muscle actin, which displays excessive adhesive properties. The precise contribution of adhesive signalling, which involves integrinmediated activation of focal adhesion kinase (FAK)/src, to the fibrotic phenotype of cutaneous SSc fibroblasts is unclear. Methods. Fibroblasts (n ¼ 6) and skin biopsies were obtained from control and SSc tissue, and derived from mouse embryonic and mouse integrin b1 wild-type and knockout. Proteins and RNAs including phospho-FAK, FAK, CCN2, vinculin, a-SMA and Type I collagen antibodies were examined by IF staining, RT-PCR and western blot analysis. Cells were incubated for 24 h in the presence or absence of anti-integrin b1 antibody, N-acetyl cysteine (NAC) or PP2 (10 mM). In addition, the ability matrix remodelling in collagen contraction models and migration assays were also examined.Results. Histological analysis of SSc dermal tissues reveals differential expression of p-FAK protein compared with control dermis. FAK phosphorylation was found to be reduced in integrin b1 knockout mouse dermal fibroblasts. Neutralizing anti-integrin b1 antibody or the anti-oxidant NAC reduces FAK phosphorylation in SSc fibroblasts. These results show integrin b1 and reactive oxygen species (ROS) are required for the elevated FAK phosphorylation in SSc fibroblasts. The FAK/src inhibitor PP2 significantly decreases expression of pro-fibrotic mRNAs and proteins in normal and SSc dermal fibroblasts, such as CCN2, a-SMA and Type I collagen (P < 0.05). When normal and SSc fibroblasts were subjected to the floating collagen gel model of ECM contraction and the scratch wound assay of cell migration, in the presence or absence of PP2 and anti-integrin b1 antibody, both of them reduced the enhanced ability of SSc fibroblasts to contract a collagen gel matrix and migration. Conclusion. These results suggest that the excessive adhesion of SSc fibroblasts to ECM is intimately involved with the fibrotic phenotype of this cell type; blocking adhesive signalling may be beneficial in controlling fibrosis.