Background: Mesenchymal stem cells have delivered new approaches to the management of burn healing in severe skin injuries. Aim of the work: To evaluate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on healing of induced deep 2nd degree skin burns in albino rats. Methodology: 55 male albino rats weighed 200gm were divided into 5 groups, 5 animals in group I (control) and group II (burn model), 15 animals in group III (untreated), group IV and group V (MSCs treated). Groups III, IV and V were subdivided into 3 subgroups that were sacrificed after 7, 14 and 21 days respectively. Deep 2nd degree burn wounds were induced on a 4 cm2 area on the back of rats in groups II, III, IV and V by brass probes stabilized at 88–90°C and contacted to the shaved dorsal skin of rats for 20 seconds without exerting any external pressure. Mesenchymal stem cells were isolated from the bone marrow of 5 young rats, weighed 100gm then intra-dermally and intraperitoneally injected. Results: By the end of the third week, the wounds of BMSCs-treated groups showed full regeneration of epidermis, re-organization of collagen and decrease in VEGF immunopositive cells. Delayed wound healing was seen in 20% of systemically treated rats. Significant increase in the mean area percent of collagen fibers was detected in topically treated group. Conclusion: Both methods of BMSCs injection were effective in healing of full thickness skin wound but topical method was more effective.