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Objectives/Hypothesis. Proper wound healing following endoscopic sinus surgery (ESS) is influenced by several factors, like cigarette smoke (CS) exposure. This study aims to assess the influence of cigarette smoke on the healing of induced septal mucosal lesion in rats. Methods. Unilateral nasal wounds were created by means of the interdental brush in seventy-four-week-old male rats. Animals were randomly divided into two groups: control group and CS exposure group, each comprising 35 animals, divided into five groups (n = 7). Animals were sacrificed in groups of seven on day 2 and then on days 5, 14, and 28 and finally on day 42 following wound induction. Results. Histological analysis of mucosal specimens shows important changes at the CS exposure group. Starting with the infiltrates of neutrophils, eosinophils, macrophages, and lymphocytes, the histological changes were continued with the Goblet cell proliferation, ciliated cells loss, fibrosis, and epithelial and subepithelial hypertrophy. Conclusion. In this experimental model of nasal wound healing we demonstrated the deleterious effects of chronic CS exposure. The adverse effects of CS exposure are firstly a postponement of the healing process and secondly the persistence of inflammation which becomes chronic.