Introduction: Ulcer is a common oral lesion, characterized by the excavation of mucosal epithelial tissue and caus- ing pain.Citrus aurantifolia Swingle peel extract contains flavonoids as an anti-inflammatory in the wound healing process. The elasticity of the nanotransfersome increases flexibility across mucous membranes. This study aimed to determine the effect of topical Citrus aurantifolia Swingle peel extract nanotransfersome gel on macrophages in labial ulcers of rats. Methods: Preparation nanotransfersome gel of Citrus aurantifolia Swingle peel extract by sonication method. Randomized Post Test Only Control Group with time series on days 3 and 7 (32 rats), with the division: group K (control), P1 (given nanotransfersome gel of Citrus aurantifolia Swingle peel extract), P2 (given Citrus auran- tifolia Swingle peel extract), and P3 (given herbal medicine with aloe vera gel standard). Applications on mucosal wounds are carried out in the morning and evening. Macrophage cell count with Hematoxylin Eosin (HE) staining with 400x magnification/ five fields of view. Results: The results of the Independent T-Test, One Way ANOVA, and Post Hoc Tukey test showed a significant difference in the number of macrophage cells between each group (p<0.05) and the results of the Pearson test showed a positive correlation on the third day and a negative correlation on the seventh day (p<0.05). Conclusion: Citrus aurantifolia Swingle peel extract nanotransfersome gel topically has an effect on macrophages on the healing process of labial ulcers.