Phosphatidylcholine (PC) is a main component of the hydrophobic gastric mucosal barrier. Exogenously administered, it prevents acute lesions. We evaluated the gastroprotective capacity of exogenous PC in both acute (ethanol- and indomethacin-induced) and chronic (indomethacin-induced) lesions in rats. Polyunsaturated (PPC) or hydrogenated PC in different concentrations were given intragastrically, before or after the injury factor, in single or repeated doses. Mucosal lesions were significantly reduced by a single dose of PPC, given before or after the injury factor, in both acute models. In the chronic model a single dose of PPC or hydrogenated PC significantly reduced lesions evaluated 6 h after ulcer induction, whereas after 72 h no protective effect was noticed. Repeated doses of PC were ineffective. In conclusion, in acute models exogenous PC reduces lesions in a dose-dependent manner and contributes to the mucosal defense. In chronic models an incomplete and temporary protection might be due to complex pathogenesis that requires activation of all levels in the mucosal defense. Strengthening of only one level was insufficient to restrict injury.