Background: Secondary lymphedema is a life-long disease of painful tissue swelling that often follows axillary lymph node dissection to treat breast cancer. It is hypothesized that poor lymphatic regeneration across the obstructive scar tissue during the wound healing process may predispose the tissue to swell at a later date. Treatment for lymphedema remains suboptimal and is in most cases palliative. The purpose of this study was to evaluate the ability of Lymphomyosot to treat tissue swelling and promote lymphangiogenesis in experimental models of murine lymphedema. Methods: Experimental models of mouse lymphedema were injected with varied amounts of Lymphomyosot and saline as control. Measurements of tail swelling and wound closure were taken and compared amongst the groups. Three separate groups of mice were analyzed for lymphatic capillary migration, lymphatic vessel regeneration, and macrophage recruitment. Results: Lymphomyosot significantly reduced swelling and increased the rate of surgical wound closure. Lymphomyosot did not increase the migration of lymph capillaries in a mouse tail skin regeneration model or regeneration of lymph vessels following murine axillary lymph node dissection. Conclusions: Lymphomyosot may act through inflammatory and wound repair pathways to reduce experimental lymphedema. Its ability to regulate inflammation as well as assist in tissue repair and extracellular formation may allow for the production of a scar-free matrix bridge through which migrating cells and accumulated interstitial fluid can freely spread.