The main pathological condition in patients with impaired wound healing is diabetes mellitus. These patients have significantly low circulating nitric oxide (NO) levels because the stimulatory action of insulin on NO synthesis is absent. Additionally, asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, is increased owing to the generation of oxidative stress. NO was thought to contribute to wound healing. Hyperbaric oxygen (HBO) treatment is generally used in order to accelerate the healing of wounds. The aim of this study was to determine the changes in plasma procollagen type I and III N-terminal peptides (PINP and PIIINP), total nitrite/nitrate (NO(x)) and ADMA levels; and to evaluate their relation to healing during the HBO treatment of foot ulcers. Data obtained from 18 diabetic patients before and after the HBO therapy were compared statistically by the Wilcoxon test. NO(x) was increased in 11 and ADMA was decreased in 12 patients following HBO treatment. Both PINP (32.6 +/- 29.4 microg/l vs 44.3 +/- 33.4 microg/l) and PIIINP (6.97 +/- 3.01 microg/l vs 7.92 +/- 2.49 microg/l) were significantly increased (p < 0.05). Progressive reductions were observed in wound areas, as assessed by the digital wound imaging. In 12 patients, wounds healed by 50% or higher; whereas only two subjects had minimal improvements (15% or less healing). The duration of diabetes correlated negatively with wound healing (r = -498, p < 0.05). This study suggests that increased collagen synthesis is associated with wound healing during hyperbaric oxygen therapy. Nitric oxide generation may also contribute to the healing process.