Aim To investigate the effect of miR-92a-3p_R +1 and miR-92a-1-5p on phenotypic transformation and proliferation of rat vascular smooth muscle cells (VSMC) induced by oxidized low-density lipoprotein (ox-LDL) in the ERK 1/2 signaling pathway. Methods VSMC isolated from rats, and ox-LDL (50 mg/L) was used to induce VSMC.ERK1/2 inhibitors U0126(10 μmol/L)was used for intervention. The miRNA microarray profiling was performed using small RNA sequencing analysis. CCK-8 method and Brdu flow cytometry were used to detect VSMC proliferation. Immunofluorescence assay was performed to detect the expression of SM22α protein in VSMC. Western blot was used to detect the expression changes of ERK1/2 pathway signal molecules (ERK, p-ERK), phenotype marker protein SM22α and proliferation associated proteins such as PCNA, cyclin D1, p21 and p27. Results Under ox-LDL induction, the expressions of miR-92a-3p_R +1 and miR-92a-1-5p in VSMC were significantly up-regulated. After the intervention of ERK1/2 inhibitors U0126, the phosphorylation level of ERK1/2 was inhibited, the corresponding VSMC miR-92a-3p_R +1 and miR-92a-1-5p expression significantly lowered (P<0.05). Therefore, the study speculated that ERK1/2 signaling pathway may affect the phenotypic transformation and proliferation of VSMC by regulating the expression of miR-92a. After inhibiting the ERK1/2 signaling pathway, the proliferation of VSMC was significantly reduced, and the expression of SM22α was up-regulated (P<0.05). The expression of PCNA and cyclin D1 was down-regulated and the expression of p21 and p27 proteins were up-regulated (P<0.05). This indicated that the phenotypic transformation and proliferation were significantly inhibited. Conclusion Mir-92a-3p_R +1 and miR-92a-1-5p play important roles in the ERK1/ 2 signaling pathway that ox-LDL induces phenotypic transformation and proliferation of VSMC.