Background: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-β<sub>1</sub> also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-β<sub>1</sub> examining the latent/mature form of TGF-β<sub>1</sub> and the presence of mast cells. Effects of age were also evaluated. Methods: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-β<sub>1</sub>/anti-TGF-β<sub>1</sub> antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining. Results:Latent TGF-β<sub>1</sub> was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-β<sub>1</sub> significantly differed between healthy and varicose veins. No mature TGF-β<sub>1</sub> was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-β<sub>1</sub>. Conclusion: Aging and varicose pathology induce dysregulation of TGF-β<sub>1</sub> that could play an important role in the fibrous process, representing the final stages of venous insufficiency.