Background: Oral submucous fibrosis (OSF) is a premalignant fibrotic oral disease. The aim of this study was to investigate the relationship between fibrosis and the expression of TGF-β1, MMP-1, and TIMP-1 and epithelial dysplasia in OSF. Methods: Forty-two tissue samples from the oral mucosa of OSF patients were histopathologically and immunohistochemically examined. The expressions of TGF-β1, TIMP-1, MMP-1 and PCNA were observed using immunohistochemistry. Results: Compared to normal oral mucosa (NOM), MMP-1 expression was attenuated in OSF while TGF-β1 expression was upregulated (P<0.05). TIMP-1 expression of OSF was slightly elevated or similar to NOM. Proliferating activity was correspondingly increased in dysplastic OSF and was found to be statistically significant (P<0.05). No significant relationship was found between epithelial dysplasia and expressions of TGF-β1, MMP-1, and TIMP-1 in OSF. Furthermore, the relationship between epithelial dysplasia and the degree of fibrosis failed to show any positive correlation in OSF. Conclusions: This study provides further evidence that the fibrotic process in OSF is not only due to excessive collagen deposition but also due to disequilibrium in the ECM remodeling process. Neither the ECM remodeling process nor tissue fibrosis of OSF directly shows any significant effect on epithelial dysplasia.