Crocetin, a carotenoid isolated from the Chinese herbal medicine Crocus sativus L. (Saffron), has been shown to have cardiovascular protective effects. The present study investigated the protective action of the antioxidant crocetin against cardiac hypertrophy induced by norepinephrine (NE). This was evaluated by assaying for pathological histological changes with an optical microscope and cell image analysis system. Lipid peroxidation was quantified using thiobarbituric acid-reactive substances (TBARS). Myocardial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myocardial catalase (CAT) activities were assayed to evaluate the antioxidant capacity. After long term treatment with NE, antioxidant enzymatic activities were significantly decreased, while products of lipid peroxidation increased. Crocetin markedly reduced the content of lipid peroxidation (LPO), increased the GSH-Px and SOD activity in cardiac hypertrophy, and significantly improved the myocardial pathological histological changes induced by NE. These results suggest that the cardioprotective effects of crocetin are related to modulation of endogenous antioxidant enzymatic activities. Comparing crocetin with captopril, our results indicated that antioxidant activity is an important factor in the therapy of cardiac hypertrophy, but as an antioxidant only, its effects may be limited.