The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site of Herpes virus simplex infections, using microparticles as carriers. Poly(d,l-lactic–co-glycolic acid) microparticles loaded with ACV were prepared using a solvent evaporation technique. ACV distribution into porcine skin after topical application of microparticles for 6, 24 and 88 h, was determined by horizontal slicing of the skin. An ACV suspension served for comparison. The results showed that, at 6 and 24 h, the quantity of the drug in the basal epidermis with the microparticles, is similar to that obtained with the ACV suspension. However, after 88 h, the ACV reservoir in the basal epidermis was higher with the microparticles compared with the control suspension. This could be explained by the controlled drug release produced by the vector in the basal epidermis. Besides, at 88 h the amount of ACV detected in the receptor chamber of the diffusion cells was much lower with the microparticles than with the suspension. This type of carrier can improve acyclovir topical therapy since it increases drug retention in the basal epidermis and consequently increases the time intervals between doses