Purpose: We previously have shown that the vacuum assisted closure (VAC) device causes microdeformations of the wound surface in contact with the foam. Because angiogenesis and matrix metalloproteinase (MMP) activity are altered in chronic wounds, we hypothesized that VAC-induced microdeformations stimulate capillary formation and affect MMP activity. Methods: A VAC device was used to deliver microdeformational wound therapy (MDWT) to the chronic wounds of three debilitated patients. Debrided tissue was obtained from wound areas with and without foam contact. Microvessel density and MMP activity were determined by immunohistochemistry and zymography, respectively. Results: Microvessel density of MDWT treated wounds was 4.5% (+/- 0.8) compared to areas not covered by foam [1.6% (+/- 0.1)] (P= 0.05) during the first week of treatment and 2.7% (+/- 0.3) compared to non-treated tissue [1.3% (+/- 0.1)] (P=0.03) during the second treatment week. Wounds subjected to MDWT had greater microvessel density compared to the same wound prior to treatment [1.5% (+/- 0.3)] (P=0.02). MMP-9/NGAL, MMP-9, latent MMP-2 and active MMP-2 were reduced by 15%-76% in MDWT treated wounds. Conclusions: MDWT increases angiogenesis while decreasing MMP activity in chronic wounds. Providing a favorable environment for endothelial proliferation may be one mechanism by which MDWT accelerates wound healing.