Objective To explore the relationship between the expression of smooth muscle 22 alpha ( SM22α),α-smooth muscle actin (α-SMA) and the development of varicose veins of the lower extremities. Methods We collected tissues of varicose saphenous vein in the experimental group,and what left over of normal saphenous vein tissues harvested for a coronary bypass operation ( control group).RT-PCR were applied to investigate the expression level of SM22αmRNA and immunohistochemical techniques were applied to investigate the expression level of SM22α and α-SMA protein in normal and varicose veins. Results The expression level of SM22α mRNA in normal and abnormal veins was 0.2614 ±0.1168 and 0.5114 ± 0.1554 respectively ( t =5.020,P ＜ 0.01 ).The immunohistochemical staining showed that signals of SM22α and α-SMA protein existed in the cytoplasm of smooth muscle cells.The integrate optical density (IOD) of SM22α in normal and abnormal veins was 10 055 ± 3584 and 16 226 ± 3378 respectively ( t =4.991,P ＜ 0.01 ).The IOD of α-SMA in normal and abnormal veins was 9746 ± 3903 and 15 371 ± 4318 respectively (t =3.861,P ＜ 0.05 ). Conclusions SM22α and α-SMA was down-regulated in varicose veins,indicating that the VSMC had transformed the typical contractile phenotype into the typical synthetic phenotype.Phenotype changes of VSMC further promote venous wall remodeling leading to the occurrence of varicose veins.