The objective of the research was to develop and evaluate ibuprofen (Ibu) loaded spanlastics as an efficient wound healing treatment. Ibu- loaded vesicles were prepared employing ethanol injection technique using three edge activators; Tego® care 450, Cremophor RH 40 and Crodafos™ CES along with Span 60. Entrapment efficiency percentage (EE%), vesicular size and zeta potential were evaluated to select the optimal formulations. In- vitro release study, differential scanning calorimetry, xray diffraction and transmission electron microscopy were performed. Selected formulations were incorporated in a hydrogel to assess their in-vivo wound healing efficiency using full-thickness wound model. The vesicles exhibited high EE% (60.6-93.9 %), particle size ranged from 114.8 to 663.5 nm and zeta potential was from -26.2 to -42.3 mV which indicated good stability. In-vitro release pattern was biphasic. In-vivo assessment of wound healing efficacy of selected Ibu-loaded spanlastics disclosed significant reduction of wound size. A significant inhibition in TNF-α secretion as well as increased production of VEGF and Col-1 were noticed in rats treated with topical application of Ibu-spanlastics and an almost normal histological structure was observed in their microphotographs. These results confirmed that spanlastics might be a peculiar delivery system for Ibu to improve its topical wound healing efficacy.