Background: Burn injuries remain a global health concern, with third-degree burns posing high morbidity and mortality risks. Effective wound healing requires both regeneration and inflammation control. Hypoxia-induced mesenchymal stem cell-derived exosomes (EH-MSCs) have emerged as a promising cell-free therapy due to their regenerative and immunomodulatory properties.Objective: This study aimed to evaluate the effect of EH-MSCs on the expression of Platelet-Derived Growth Factor (PDGF) and Interleukin-10 (IL-10) in a Wistar rat model of third-degree burns.Methods: An experimental study with a Post-Test Only Control Group design was conducted at the Stem Cell and Cancer Research Laboratory, Sultan Agung Islamic University, Semarang, in April 2025. Thirty male Wistar rats (6–8 weeks, 200–250 g) were randomized into five groups: healthy control, burn + NaCl, burn + silver sulfadiazine, burn + EH-MSC 100 µg/mL, and burn + EH-MSC 200 µg/mL. Third-degree burns were induced using a 2 × 2 cm² pre-heated metal plate under ether anesthesia. EH-MSCs were isolated from rat umbilical cords using tangential flow filtration and validated with CD63 and CD9 markers. On day 5, PDGF and IL-10 expressions were measured via RT-PCR after orbital sinus blood sampling. Data were analyzed using Shapiro-Wilk and Levene’s tests, followed by One-Way ANOVA or non-parametric equivalents, with p<0.05 considered significant.Results: PDGF and IL-10 expression increased in EH-MSC-treated groups, with the highest levels in the 200 µg/mL dose. IL-10 showed a significant difference among groups (p = 0.030), and post hoc tests confirmed higher expression in EH-MSC groups. PDGF showed a significant pairwise difference, though overall ANOVA was not significant (p = 0.094).Conclusion: EH-MSCs significantly enhanced IL-10 expression and increased PDGF levels, supporting their potential to promote regeneration and modulate inflammation in burn wound healing.