Normal wound healing is a complex and dynamic process. Wound healing process can accelerate, with chemical treatment or natural. The chemical treatment often used in healing process is povidone iodine. For natural treatment, topical application of Aloe vera gel may accelerate the full-thickness wound healing process. The purpose of this research was to evaluate the differences between topical application of povidone iodine and Aloe vera gel for skin wound healing in mice. This study used 18 mice that were divided into three groups. First group was the wounded (control) group, the second group was wounded - Aloe vera group, the third group was wounded -povidone iodine group. Full-thickness skin wound were created on the dorsal area of mice in each group. The control group were not given anything, while the second group were given Aloe vera gel twice a day, and the third group were given povidone iodine solution twice a day. At the fifth day, all mice were sacrificed for histologic evaluation and VEGF A expression. Data was obtained by microscopic observation of the wounded skin, based on quantitative parameter: epithelial thickness, total fibroblast, total blood vessels, and VEGF A expression. Then the data was statistically analyzed by using independent samples T test, ANOVA, and Chi square. The result demonstrated that the sum of epithelial thickness, fibroblast, blood vessels, and VEGF A expression in the Aloe vera group is higher than in povidone iodine group. Statistic evaluation showed that there were significant differences between the two groups (p < 0.05), with 95% confidence interval. Based on this result, it can be concluded that the topical administration of Aloe vera gel twice a day is better than povidone iodine with parameter epithelial thickness, total fibroblass, total blood vessels and VEGF A expression.