Much of the beneficial effects of tomato lycopene in the prevention of chronic diseases has been attributed to its antioxidant properties, which could be mediated by its metabolites and/or oxidation products. However, the biological functions of these lycopene derivatives remain still unknown. In the present study, we evaluated and compared the antioxidant efficacy of the lycopene eccentric cleavage products apo-10'-lycopenoic acid and apo-14'-lycopenoic acid in counteracting the oxidative effects of H2O2 and cigarette smoke extract (CSE) in THP-1 macrophages. Both apo-10'lycopenoic acid and apo-14'-lycopenoic acid were able to inhibit spontaneous and H2O2-induced ROS production in a dose-dependent manner. Such an effect was accompanied by an inhibition of MAPK phosphorylation, by NF-kB inactivation, and by inhibition of hsp-70 and hsp-90 expressions. Both apo-lycopenoic acids also decreased CSE- induced ROS production, 8-OHdG formation and reduced the increase in NOX-4 and COX-2 expressions 35 caused by CSE. However, in both the models of oxidative stress, apo-14'-lycopenoic acid was much more potent as an antioxidant than apo-10'-lycopenoic acid, showing antioxidant properties similar to lycopene. These data strongly suggest that apo-lycopenoic acids, and particularly apo-14'-lycopenoic acid, may mediate some of the antioxidant functions of lycopene in cells.