Intralesional injection of triamcinolone (TMC) preparations is an effective therapy for cystic acne lesions. However, invasive delivery techniques limit the use of this modality to a relatively narrow class of cases. Skin permeability can be enhanced through creating a lattice of microzones (islets) of light-induced limited thermal damage in the upper layers of epidermis. In this paper, we directly compared safety and efficacy of delivering TMC acetonide with this novel technique versus conventional intralesional injection for treatment of inflammatory acne lesions. A combination of an intense pulsed light system and a specially designed appliqu′e with a pattern of absorbing centers has been used to create the lattice of islets of damage (LID). Quantitative analysis has included estimation of the following parameters: redness, diameter, and height of acne lesions. Clinical photography has been used to document dynamics of lesion development at successive visits (two hours, 24 hours and one week post-treatment). Seven subjects have participated in the study. No difference in lesion dynamics between the treatment and control groups was observed at two-hours follow-up. At 24-hours/one-week follow-ups, TMC-injected and TMC-LID-delivered groups have demonstrated 82%/93% and 80%/89% improvement in height of lesions in comparison to control (60%/68%). Delivery of TMC with the newly proposed LID technique is at least as effective as intralesional injection for treating inflammatory acne lesions. Enhancement of skin permeability using LID approach is a promising technique for accelerating delivery of various compounds to their target areas in the skin.