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The use of natural materials as wound healing is an alternative that is widely used. Red Dragon Fruit Extract (EBNM) has antioxidant and anti-inflammatory content that is needed to accelerate the wound healing, but studies have reported effects on wound healing is still limited. The purpose of this study was to evaluate the effect of topical Red Dragon Fruit Extract on DM wound and Non-DM wound healing in Wistar rats. This research method is an Experimental Study with post-test with control group design. Albino Male Wistar rat (n = 18) with the weight (200-250 grams) were divided into 2 groups (group A (n = 9) Wistar DM + incision divided into 3 groups, each with 3 rats and group B (n = 9) Non-DM Wistar + incision divided into 3 groups of each 3 rats). Furthermore Wistar rat wounded in the back left and right using 8 mm punch biopsy. 7.5% topical Red Dragon Fruit Extract cream was applied to the surface of the wound with the cotton bud. Tissue preparat colored with Hematoxylin and Eosin (HE) then the wound healing parameters were assessed; the thickness of the granulation tissue and epithelialization with histopathology assessment. Data were analyzed using independent T test and paired T test (SPSS 21, Chicago Inc.) Granulation scores tend to be better at a concentration of 7.5% in the topical Red Dragon Fruit Extract than the negative control group for DM (p <0.068) and non-DM (p <0.034). Epithelialization Scores are better at concentrations of 7.5% in Topical Red Dragon Fruit Extract group than the negative control group for DM (p <0.034) and non DM (p <0.034). Topical Red Dragon Fruit Extract 7.5% increase the growth of granulation tissue and epithelialization in wound healing of acute non-DM and DM at Wistar rats.