BACKGROUND: Kaurenoic acid (KA), a diterpene extracted from copaíba oil-resin, is known to have potent antioxidant and anti-inflammatory properties. L-Arginine (LA) is an amino acid and a nitrogenous precursor for the synthesis of nitric oxide (NO). NO paper in wound healing has already been well documented. The aim of this study was to investigate the protective effects of LA and KA against ischemia reperfusion injury in a randomized skin flap model in rats. METHODS: A modified McFarlane flap model measuring 2.5 wide × 8 cm long was established in 36 anesthetized rats and evaluated within 3 groups: group control, group L-arginine, and group kaurenoic acid. Each group was subdivided into two subgroups (T1 and T2, n = 6 each). Samples were collected 24 h (T1)/48 h (T2) postoperatively for oxidative stress (glutathione), as non-protein thiols, malondialdehyde (MDA), NO2, inflammation [myeloperoxidase (MPO)], and cytokines TNF-α and IL-1ß assays. RESULTS: KA promoted a significant decrease of TNF-α and IL-1 expression and MPO activity at T1/T2 time points. NSGH levels increased significantly in KA-treated rats, while MDA levels decreased significantly in the same rats. Arginine promoted a significant decrease in MDA levels at the T1 time point and a significant increase in non-protein thiols concentrations at T1/T2 time points. NO2 concentration also decreased at the T1 time point. CONCLUSIONS: KA may attenuate the oxidative stress and the inflammation, thereby reducing tissue damage induced by ischemia/reperfusion in rats subjected to dorsal skin flaps. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.