AIMS: Resveratrol, a silent information regulator 1 (SIRT1) activator, has been reported to act as an antioxidant contained in red wine and prevent the development of cardiovascular diseases. Histone deacetylase such as SIRT1 is involved in the regulation of lifespan extension. In this study, the effect of resveratrol on matrix metalloproteinases (MMPs) that play an important role in metastasis was examined in human fibrosarcoma cell line, HT1080. MAIN METHODS: The effect of resveratrol on MMPs' activity was evaluated using gelatin zymography. Western blot analysis and RT-PCR assay were used to determine the effect of resveratrol on the expression level of MMP-9, MAPK and SIRT1 proteins and genes, respectively. KEY FINDINGS: It was observed that resveratrol exhibited not only antioxidant effects on lipid peroxidation and DNA oxidation but also inhibitory effects on the expression of MMP-2 and 9 in HT1080 cells stimulated with either phorbol myristate acetate or phenazine methosulfate. Furthermore, it was found that treatment with resveratrol decreased the level of MMP-9 expression via down-regulation of p-ERK, c-fos and p65. In addition, the level of SIRT1 gene expression was also enhanced by treatment of resveratrol alone but the level of MMP-9 gene expression was decreased. SIGNIFICANCE: These results suggest that the activation of SIRT1 in the presence of resveratrol especially inhibits the expression of MMP-9 in HT1080 cells, providing evidence that resveratrol can be a potential candidate for chemoprevention of cancer.