Objective To investigate the effect of the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) on the injury of rat vascular smooth muscle cells (VSMCs) induced by oxidative stress. Methods Rat aortic VSMCs were cultured and divided into control group, oxidative damage group, Nrf2 activation group and Nrf2 siRNA-expressing lentiviral vector (Nrf2 siRNA) group. Protein level of Nrf2 was determined by Western blotting. Cell viability was measured by MTT assay, and cell apoptosis was determined by Hoechst 33342 and Annexin V/FITC. Results VSMCs were transiently transfected with Nrf2 siRNA. Nrf2 siRNA significantly inhibited the expression of Nrf2 at protein level compared to the control(P＜0.05). Compared to oxidative damage group, cell viability was significantly increased (P＜0.05) and cell apoptosis was decreased in Nrf2 activation group(P＜0.05). However, compared to oxidative damage group, cell viability was significantly decreased (P＜0.05) and cell apoptosis was increased in Nrf2 siRNA group(P＜0.05). Conclusion Nrf2 activation can reduce oxidative stress-induced damage inVSMCs.