Animal studies report photodynamic therapy (PDT) to improve healing of excisional wounds but the mechanism is uncertain and equivalent human studies are lacking. To explore the impact of methyl aminolaevulinate (MAL)-PDT on clinical and microscopic parameters of human cutaneous excisional wound healing, examining for potential modulation through production of transforming growth factor (TGF)-β isoforms. In healthy older men (60-77 years; n=27), a 4 mm punch biopsy wound was created in skin of the upper inner arm and treated with MAL-PDT three times over five days. An identical control wound to the contralateral arm was untreated and both wounds left to heal by secondary intention. Wounds were re-excised at time points examining the inflammatory phase (7 days, n=10), matrix remodelling (3 weeks, n=8) and cosmetic outcome/dermal structure (9 months, n=9). Production of TGF-β1, TGF-β3 and matrix metalloproteinases (MMPs), key mediators of matrix deposition and remodelling, was assessed by immunohistochemistry alongside microscopic measurement of wound size/area and clinical assessment of wound appearance. MAL-PDT delayed re-epithelialisation at 7 days, associated with increased inflammation. However, 3 weeks post-wounding, treated wounds were smaller with higher production of MMP-1 (P=0.01), MMP-9 (P=0.04) and the anti-scarring cytokine, TGF-β3 (P=0.03). TGF-β1 was lower than control at 7 days and higher at 3 weeks (both P=0.03). At 9 months MAL-PDT treated wounds showed greater, more ordered deposition of collagen I, collagen III and elastin (all P