To achieve an efficient approach for burn regeneration, we aimed to investigate the effects of encapsulated human umbilical cord-derived mesenchymal stem cells (hUMSCs) in platelet-rich plasma cryogel (PRPCryogel) on regeneration of grade-II burn wounds in a rat model. MSCs were extracted from the umbilical cord and characterized by flow cytometry. Forty rats were divided into 4 groups including PRPCryogel-MSCs, PRPCryogel, MSCs, and control treatment. After 7, 14, 21, and 28 days post-treatment, the wound sites were photographed and wound samples were taken. H&E staining for wound samples was done to assess re-epithelialization, angiogenesis, and formation of granulated tissue. The gene expression rates of Ang-1 and VEGF growth factors were also determined by qRT-PCR. The higher wound closure rate was seen for the PRPCryogel-MSCs group on day 21 and 28 compared to other groups. Based on H&E results, an ascending rate of re-epithelialization was seen for the PRPCryogel-MSCs group on day 28. The most angiogenesis rate was detected for MSCs and PRPCryogel-MSCs groups on day 14. The qRT-PCR results showed the peak expression rate of Ang-1 in PRPCryogel-MSCs and MSCs groups on day 14. The peak expression rate of VEGF was also seen for PRPCryogel-MSCs and PRPCryogel groups on day 28. The treatment of burn wounds with PRPCryogel-MSCs promoted the wound closure and re-epithelialization rates. It also increased the expression rate of Ang-1 and VEGF genes which is consistent with pathological assessments. In conclusion, combination of MSCs with PRP can be considered as a promising approach for burn healing. Application of different natural substances for wound healing returns to a long period of time ago. Nature has been always generous and among these, mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are such prominent gifts. MSCs have been well-identified for tissue regeneration which can be derived from bone marrow, umbilical cord, adipose tissue, etc. By differentiation into key cells such as fibroblasts and keratinocytes, contributing in vascularization, re-epithelialization, and collagen synthesis, MSCs accelerate the regeneration of damaged tissue. PRP is another spectacular substance derived from blood which is a rich suspension of platelets, growth factors with pain relieving and antimicrobial effects. We assessed the effects of MSCs which were placed within the PRP gel (PRPCryogel) on healing of grade-II burn wounds. Results showed that PRPCryogel-MSCs promote burn healing by increasing the rate of wound closure, angiogenesis, and re-epithelialization compared to other groups. This verifies the impressive effects of MSCs with PRP when combined together for burn treatment. Finally, this method can be also examined on regeneration of grade-III burn and/or chronic wounds as a future study in this field.