Pycnogenol (PYC), an extract of pine bark, is known to have photoprotective, antimicrobial, antioxidant, and anti-inflammatory properties. An in vivo study was conducted to evaluate the effects of PYC treatment on wound healing in 48 adult male Sprague-Dawley rats, of which 24 were injected with a single dose of alloxan to induce diabetes.Three (3) excisional skin wounds (1.3 cm x 1.3 cm x 2 mm) were created in each healthy and diabetic animal. One (1) wound in each animal was left untreated, 1 was treated daily with a cleanser (ethacridine lactate) and covered with silver sulfadiazine (SSD), and 1 was treated with PYC powder (30 mg). After measuring wound size, 6 animals from both groups were sacrificed on days 3, 7, 14, and 21 and tissue samples were taken for histopathological evaluation of acute and chronic inflammation, granulation tissue, fibroblast maturation, collagen deposition, epithelialization, and neovascularization using a scoring system of 0 = none, 1 = mild, 2 = moderate, and 3 = abundant. Because the wounds created were not uniform in size within and among the animals, healing was expressed as a percentage of the initial wound size for each animal. Data were compared using 2-way analysis of variance; histopathological lesion scores were reported in median values in univariate analysis, with P <.05 denoting statistical significance. The mean initial wound surface area was 1.69 ± 0.44 cm2. On day 21, the average reduction in wound size was lower in diabetic than in healthy rats (47.42% versus 50.91%, P <.0001) and, in both groups combined, the average reduction was 45.73% in untreated, 48.73% in cleanser/SSD-treated, and 58.03% in PYC-treated wounds (P <.0001). Wound size reduction was also significantly different between PYC and the cleanser/SSD treatment depending on the rats’ health status (P <.0001): 49.68% and 47.84% using cleanser/SSD and 56.17% and 49.84% using PYC in healthy and diabetic rats, respectively. After 3 weeks, wound size for the healthy rats had decreased more than in the diabetic rats (mean 50.91% versus 47.42%). Although reepithelialization was complete in both groups by day 21, complete neovascularization was evident in the healthy rats but not in the diabetic rats. Overall, compared to the untreated control wounds, treatments with cleanser/SSD and PYC were equally effective in lowering acute and chronic inflammation scores on days 7 and 21. In diabetic rat wounds, collagen deposition and neovascularization scores were higher in wounds treated with PYC than cleanser/SSD-treated wounds (1.5 versus 1.0 and 2.0 versus 1.5, respectively). PYC appears to be a viable option to accelerate wound healing. Further in vivo and human research is warranted.