The present study aimed to detect and verify gene expression profile differences for microRNA (miR)‑146a and its role in the proliferation of vascular smooth muscle cells (VSMCs). Artificially synthesized miR‑146a mimics, miR‑146 inhibitor, scramble‑miRNA or PBS was transfected into cultured primary rat VSMCs in vitro. Reverse transcription‑quantitative polymerase chain reaction confirmed that the miR‑146a expression level was significantly decreased in VSMCs treated with miR‑146a inhibitor (P<0.01). Cell Counting Kit‑8 was used to determine the proliferation ability, which demonstrated that proliferation was significantly decreased in VSMCs treated with miR‑146a inhibitor (P<0.01). Microarray expression profiling analysis revealed that the p53 signal pathway was upregulated in VSMCs treated with the miR‑146a inhibitor. Compared with untransfected VSMCs, the mRNA and protein expression levels of caspase‑3 and phosphatase and tensin homolog (PTEN) in p53 signal transduction pathway did not exhibit a significant difference (P>0.05); however, the mRNA and protein expression levels of p53 were significantly decreased in cells transfected with miR‑146a mimics and increased in miR‑146a inhibitor transfected cells (both P<0.01). The mRNA and protein expression levels of cyclin D1 significantly increased in miR‑146a mimics transfected cells and decreased in cells transfected with the miR‑146a inhibitor (both P<0.05). The present data indicated that miR‑146a may promote the proliferation of rat VSMCs by downregulating p53 and upregulating cyclin D1 expression.