Purpose: Although varicose veins are common, the primary cause predisposing to venous reflux of great saphenous vein is controversial. We compared histologic features and expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in the great saphenous veins (GSVs) of normal and patients with varicose veins. Method: Ten normal proximal GSV and each twenty diseased proximal, mid, and distal above-knee GSV vein segments were used for this analysis. We compared venous architecture with histology and expression and localization of MMP and TIMP with immunohistochemistry. Result: Compared with normal veins, varicose veins showed thickening and disorganization of intimal and medial connective tissue elements. Elastic fibers of varicose vein were fragmented and degenerated. By the immunohistochemistry, MMP-1 and MMP-2 were more strongly expressed than MMP-9, TIMP-1 and TIMP-2 either normal and varicose veins. MMPs were localized to endothelial cells, medial connective tissues and adventitial microvessels in normal veins. Whereas they were more diffusely localized to subintimal and medial connective tissues in varicose veins. Compared with proximal varicose veins, TIMP-2 was more significantly expressed in distal varicose veins. Conclusion: In varicose veins, vein wall architectures are disorganized and MMPs are more prominently expressed in these degenerative subintimal and medial areas.