Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We evaluated the effect of L-AST on a phthalic anhydride (PA)-induced animal model of AD by analyzing morphological and histopathological changes. We measured the mRNA levels of AD-related cytokines in skin tissue and immunoglobulin E concentrations in the serum. Oxidative stress and transcriptional activities of signal transducer and activator of transcription 3 (STAT3) and nuclear factor (NF)-κB were analyzed via western blotting and enzyme-linked immunosorbent assay. PA-induced dermatitis severity, epidermal thickening, and infiltration of mast cells in skin tissues were ameliorated by L-AST treatment. L-AST suppressed AD-related inflammatory mediators and the inflammation markers, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in PA-induced skin conditions. Oxidative stress and expression of antioxidant proteins, glutathione peroxidase-1 (GPx-1) and heme oxygenase-1 (HO-1), were recovered by L-AST treatment in skin tissues from PA-induced mice. L-AST treatment reduced transcriptional activity of STAT3 and NF-κB in PA-induced skin tissues. Our results indicate that L-AST could be more effective than free AST for AD therapy.