Background: Bilateral mucoperichondrial flap elevation is often needed to properly correct the septal deformity although it has been discouraged because of possible complications. This study investigated the effect of unilateral versus bilateral mucoperichondrial flap elevation on the morphological and histological changes of the septal cartilage in a rabbit model. Methods: Eighteen mature New Zealand white rabbits were categorized into three groups (six animals for each) according to the procedures they received: unilateral mucoperichondrial flap elevation versus bilateral mucoperichondrial flap elevation versus no flap elevation. In each group, one-half of the animals were killed 3 months after the procedure and the other half were killed 6 months after the procedure. Thickness of cartilage was measured and histological changes of chondrocyte and extracellular matrix were evaluated using hematoxylin and eosin, Masson's trichrome, Alcian blue, and Verhoeff's elastic stains. Results: There was no difference in changes of thickness of the cartilage among the three groups. Histological examination revealed that the chondrocyte numbers and dystrophic features as well as the ratio of chondroblast were not different among three groups. Masson's trichrome stain in the bilateral group showed lesser dense collagen fibers than the other groups. Alcian blue stain for proteoglycan documented that the peripheral zone showed lower expression in the bilateral group than the other groups. However, Verhoeff's elastic stain did not differ among the three groups. Conclusion: Bilateral mucoperichondrial flap elevation of a rabbit model decreased deposition of collagen fibers and proteoglycan while maintaining the similar chondrocyte cellularity compared with the other groups.