The golden chanterelle mushroom, Cantharellus cibarius, is an edible mushroom with medicinal value. Given that this species has good radical scavenging activity and strong antioxidant potential and bactericidal effects, this study was designed to investigate the anti-inflammatory and wound-healing activity of C. cibarius extract in rats. For this experimental study, circular excision and linear incision wound models were used in 4 groups of male Wistar rats: nontreated, vehicle-treated, treated with C. cibarius extract ointment (2% w/w), and treated with the reference drug (Madecassol). All the animals were treated topically once a day. The circular and linear wounds were treated for 9 and 17 days, respectively. At the end of the study, samples from healing wounds were taken for histopathological assessment to determine the in vivo anti-inflammatory activity and investigate immunohistochemistry by cyclooxygenase-2 (COX-2). Significant wound-healing activity in each wound model was observed in the C. cibarius extract-treated and Madecassol-treated groups compared with the nontreated and vehicle-treated groups (P < 0.05). Histological assessment showed complete repair of the epidermal layer, increased collagen production, and a remarkable degree of neovascularization and epithelization in the extract group, which were significantly different from those in the other groups (P < 0.05). In addition, a significantly lower rate of COX-2 expression was detected in the extract group than in the nontreated and vehicle-treated groups (P < 0.0001). Therefore, the experimental data reveal that C. cibarius extract showed significant wound-healing and anti-inflammatory effects, which could be the scientific rationale for the medicinal use of the golden chanterelle mushroom in treating wounds.