Honey is recognized traditionally for its medicinal properties and also appreciated as a topical healing agent for infected and noninfected wounds. This study evaluates impact of honey-based occlusive dressing on nonhealing (nonresponding to conventional antibiotics) traumatic lower limb wounds (n=34) through clinicopathological and immunohistochemical (e.g., expression of p63, E-cadherin, and Collagen I and III) evaluations to enrich the scientific validation. Clinical findings noted the nonadherence of honey dressing with remarkable chemical debridement and healing progression within 11-15 days of postintervention. Histopathologically, in comparison to preintervention biopsies, the postintervention tissues of wound peripheries demonstrated gradual normalization of epithelial and connective tissue features with significant changes in p 63 + epithelial cell population, reappearance of membranous E-cadherin (P<.0001), and optimum deposition of collagen I and III (P<.0001). Thus, the present study for the first time reports the impact of honey on vital protein expressions in epithelial and connective tissues during repair of nonhealing lower limb wounds. Copyright © 2011 Ananya Barui et al.