Abstract: Background and Objective: The TGF-β1 is a multifunctional cytokine that contributes fibroplasia wound healing via mechanisms that involved free radicals. Honey has been succesfully used for treating wound healing. It’s has an antioxidant, anti-inflammatory, antibacterial and debridement effects. The antioxidant substances such as flavonoid can reduce free radicals-malondialdehyde (MDA) on rats skin wound healing. However, the mechanisms of its action at stress oxidative oral mucosa wound healing have poorly understood. The purpose of this study are to investigate the effect of rambutan-honey topical induce fibroplasia wound healing by TGF-β1 inhibit MDA formation oral mucous rats wound healing and to identify the presence of flavonoid components responsible effect. Materials and Methods: The research methods were an experimental laboratory. The samples (n = 16 group–1) were divided into negative control, positive control φ4±2 mm wound, 1 mL rambutan-honey wound and 0.1 mL ascorbic acid. Oral mucous wound were observed on day 0, 3, 7, 14. The production of TGF-β1 determined by ELISA reader. Bradford assay used for calculating protein concentration. The HPLC analysis was performed in order to identify rutin and myricetin on honey samples. The productions of free radicals were determined by MDA tissues level and fibroblast numbers that determined by histology examination and statistically analyzed (ANOVA, Tukey’s, p<0.05). Results: The results showed that rambutan-honey induce fibroplasia significantly on day 0, 3 and 7 (p = 0.001) and TGF-β1 significantly on day 3 (p = 0.008) and inhibit MDA formation significantly on day 3 (p = 0.028) and day 14 (p = 0.037). Rutin was identified flavonoid in rambutan-honey, markedly induce fibroplasia TGF-β1 inhibit MDA formation. Conclusion: Rambutan-honey that contains rutin flavonoid potentially accelerating wound healing and prevents stress oxidative induces fibroplasia by TGF-β1inhibit MDA formation. Thus, our finding provide clear evidences that rambutan-honey topical have a potential as a natural treatment for human oral mucosa wound healing.