Ultra-fine cellulose acetate (CA; Mwz30,000 Da; degree of acetyl substitutionz2.4) fiber mats containing curcumin from the plant Curcuma longa L., widely known for its anti-tumor, antioxidant, and anti-inflammatory properties, were fabricated, for the first time, from the neat CA solution (17% w/v in 2:1 v/v acetone/dimethylacetamide) containing curcumin in various amounts (i.e., 5e20 wt.% based on the weight of CA powder) by electrospinning. Incorporation of curcumin in the neat CA solution did not affect the morphology of the resulting fibers, as both the neat and the curcumin-loaded CA fibers were smooth. The average diameters of the curcumin-loaded CA fibers ranged between w314 and w340 nm. The integrity of the as-loaded curcumin in the curcumin-loaded CA fiber mats was intact as indicated by the 1H nuclear magnetic resonance spectrometric results and the ability of the as-loaded curcumin in maintaining its free radical scavenging ability. Investigation of the release characteristic of curcumin from the curcumin-loaded CA fiber mats was carried out by the total immersion and the transdermal diffusion through a pig skin method in the acetate buffer solution containing Tween 80 and methanol or the B/T/M medium at 37 C. In the total immersion method, almost all of the curcumin loaded in the curcumin-loaded CA fiber mat specimens was released into the medium (w90 to w95%), while considerably lower values were obtained when the curcumin-loaded CA fiber mats were placed on top of a piece of pig skin. Lastly, the curcumin-loaded CA fiber mats were proven non-toxic to normal human dermal fibroblasts.