Fucoidan is a sulphated polysaccharide extracted from brown seaweed and possesses a wide range of pharmacological properties including antiallergic and immunologic activities. The present study attempted to examine the effectiveness of fucoidan from Undaria pinnatifida in the treatment of atopic dermatitis (AD) in the NC/Nga mice model. Three per cent fucoidan or 0.1% dexamethasone was topically applied to the dorsal skin of AD-induced mice for 4 weeks. The dermatitis severity scores and scratch counts of fucoidan or dexamethasone-treated animals were significantly lower than the control group. Histological analysis showed that the number of mast cells infiltrating into skin lesions and the epidermis thickness were significantly decreased after the treatments. Levels of serum histamine and IgE were also decreased. There was no significant difference on improvement of AD-like symptoms between fucoidan and dexamethasone. To elucidate possible mechanism of action, effects of fucoidan on regulation of AD-associated chemokines, such as thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and regulated upon activation, normal T-cell expressed and secreted (RANTES) chemokine, were investigated in human epidermal keratinocytes. Fucoidan significantly inhibited mRNA expression of these chemokines in a dose-dependent manner. This is the first animal study to demonstrate that fucoidan has significant effects on improving AD-like conditions as effective as dexamethasone, a well-recognized corticosteroid remedy for the disease. Copyright © 2012 John Wiley & Sons, Ltd.