Aim To investigate the role of epidermal growth factor receptor (EGFR) in proliferation of vascular smooth muscle cells (VSMC) activated by angiotensin Ⅱ (AngⅡ). Methods The cultured VSMC of Sprague-Dawley rat were transfered with antisense sequences of EGFR. EGFR mRNA and protein in VSMC was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, the proliferation of VSMC was determined by 3H-deoxythymidine (3H-TdR) incorporation. Results The expression of EGFR mRNA in VSMC transfected with antisense sequences of EGFR were significantly lower than transfected with sense sequances of EGFR and control group (0.18±0.03, 0.61±0.11, and 0.66±0.09 respectively, p<0.05). The expression of EGFR protein in VSMC transfected with antisense sequences of EGFR were significantly lower than transfected with sense sequances of EGFR and control group (43.1±8.4, 92.6±10.5, and 100.7±11.3 respectively, p<0.05). The 3H-TdR incorporation of VSMC transfered with antisense sequences of EGFR were significantly lower than that transfered with sense sequances of EGFR and control group (1 055.1±95.7, 1882.4±129.7, and 2013.3±121.3 respectively, p<0.05). Conclusion EGFR play an important role in proliferation of VSMC of rat induced by angiotensin Ⅱ.