Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in neointimal formation, and therefore is suggested to contribute to arteriosclerosis and restenosis. Previous studies have suggested that some microRNAs (miRs) serve crucial roles in VSMC proliferation and invasion; however, the underlying mechanism remains largely unknown. In the present study, it was demonstrated that treatment with platelet-derived growth factor (PDGF)-BB significantly promoted the proliferation and migration of VSMCs, and decreased miR-612 levels in VSMCs. Overexpression of miR-612 significantly inhibited PDGF-BB-induced migration and invasion of VSMCs, through inducing cell cycle arrest at G1 stage. AKT2 was further identified as a direct target gene of miR-612, and its expression was negatively regulated by miR-612 in VSMCs. Further investigation confirmed that overexpression of miR-612 suppressed the PDGF-BB-induced upregulation of AKT2 protein expression. In conclusion, the present study demonstrated that miR-612 is downregulated by PDGF-BB treatment and has inhibitory effects on VSMC proliferation and migration via targeting AKT2. These findings suggest that miR-612 may be used as a potential therapeutic candidate for neointimal formation in patients with atherosclerosis.