Garcinia mangostana (mangosteen) pericarp has antibacterial effects; however, information regarding its anti-inflammatory activity in vivo is limited. The anti-inflammatory effect of G. mangostana pericarp extract against methicillin-resistant Staphylococcus aureus (MRSA)-induced superficial skin infection was investigated in mice using a tape stripping model. G. mangostana pericarp ethanolic extract (GME) and its constituent, α-mangostin, were topically administered to mice with MRSA-induced superficial skin infection. MRSA-infected wounds treated with GME were completely healed on the 10^th day of the study and the number of MRSA-colonies decreased from the first day of the study, whereas α-mangostin-treated wounds never completely healed with higher numbers of MRSA colonies. The epidermis of GME-treated wounds had nearly completely regenerated, with no inflammatory cell infiltration. In contrast, α-mangostin-treated wounds exhibited neutrophil infiltration and accumulation of mast cells. MRSA-infected wounds without treatment showed high expression of TNF-α, IL-6, IL-1β, and TLR-2 genes. In contrast, GME decreased mRNA levels, restoring expression of those genes to normal levels. Notably, α-mangostin did not down-regulate the expression of pro-inflammatory cytokines to the same extent as GME. Hence, GME is a promising alternative MRSA treatment because of its antibacterial, anti-inflammatory, and wound healing effects.