Objective To explore the effect of metformin on TNF-α-induced migration of vascular smooth muscle cells (VSMCs) and the possible mechanism. Methods VSMCs were divided into four groups: control group, TNF-α group(10 ng/mL), metformin group(2 mmol/L) and metformin+TNF-α group(2 mmol/L 10 mg/mL). The migration of VSMCs was detected by wound healing assay and transwell assay. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by RT-PCR and Western blotting analysis; the protein expression of nuclear NF-κB and cytoplasmic IκB were also determined by Western blotting analysis. Results Wound healing assay and transwell assay showed that the migration ability of VSMCs in TNF-α group was significantly increased compared with the control group (P<0.01), while that of metformin TNF-αgroup was significantly decreased (P<0.05). Compared with TNF-α group, the migration ability of metformin TNF-α group was significantly decreased (P<0.01). MMP-2, MMP-9 and NF-κB expression levels were significantly increased and the IκB expression was significantly decreased in TNF-α group compared with those in the control group (P<0.01). Compared with TNF-α group, MMP-2, MMP-9 and NF-κB expression levels were significantly decreased and IκB expression was significantly increased in metformin TNF-α group (P<0.01). The intracellular expression levels of MMP-2 and MMP-9 were significantly different between metformin group and control group (P<0.05 or P<0.01), while the intracellular NF-κB, IκB proteins were not significantly different. Conclusion It suggests that metformin can effectively inhibit the TNF-α-induced migration of VSMCs, which might be related to the down-regulation of matrix metalloproteinases and the blockage of the NF-κB signal pathway.