The present invention relates to methods of treating psoriasis by inhibiting one or more matrix metalloproteinase enzymes ("MMPs"). It is based, at least in part, on the discovery that the expression patterns of certain MMPs and related molecules are altered in patients suffering from psoriasis, relative to normal subjects. Certain expression patterns are altered even in unaffected skin of psoriasis-afflicted patients, although aberrancies are more pronounced in psoriatic lesions. In various non-limiting embodiments, the present invention provides for methods of treating psoriasis, including preventing the development of new psoriatic lesions, comprising administering, to subjects in need of such treatment, effective concentrations of compounds which inhibit the enzymatic activity of one or more MMP. Suitable inhibitors include tetracycline and its derivatives and various hydroxymate, carboxylic acid, and phosphonic acid derivatives. Therapy may comprise systemic and / or local administration of inhibitor. In additional embodiments, the present invention provides for methods of diagnosing MMP inhibitor responsive skin lesions, for evaluating the level of disease activity in a subject, and for transgenic animal and tissue culture models of psoriasis.