The role of free radicals in the development of cerulein-induced pancreatitis was evaluated by measuring the activity of the endogenous scavengers, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx), as indicators of the defense system, and the level of lipid peroxide (LPO) in the pancreas, as an indicator of the offense system. Acute pancreatitis was induced by 5 hourly intraperitoneal administrations of cerulein (50 μg/kg body weight), in 0.9% NaCl, to mice. The presence of acute pancreatitis was confirmed by changes in serum amylase levels and in typical microscopical features. Regarding the changes in the levels of endogenous scavengers, the SOD level was decreased significantly from a basal level of 52.6 ± 3.94 to 43.1 ± 2.79 mU/μg DNA at 6 h (p < 0.01) to 38.8 ± 5.18 mU/μg DNA at 9 h (p < 0.05) and to 31.7 ± 3.10 mU/μg DNA at 12 h (p < 0.01) after the first intraperitoneal cerulein injection. The CAT level also decreased significantly from a basal level of 7.80 ± 0.27 to 5.86 ± 0.46 mU/μg DNA at 9 h (p < 0.01) and to 4.52 ± 0.21 mU/μg DNA at 12 h (p < 0.01). GSHpx increased from a basal level of 6.80 ± 0.43 to 7.58 ± 0.50 mU/μg DNA at 9 h and to 10.2 ± 0.52 mU/μg DNA at 12 h after the first intraperitoneal cerulein injection. The LPO level increased from a basal level of 1.11 ± 0.48 to 7.22 ± 1.75 nmol/ml at 3.5 h(p < 0.05), 5.40 ± 1.50 nmol/ml at 6 h(p < 0.05), 3.86 ± 1.07 nmol/ml at 9 h (p < 0.05) and 3.18 ± 1.18 nmol/ml at 12 h (p < 0.01) after the first intraperitoneal cerulein injection. These results indicate that tissue imbalances of the offense system, indicated by changes in the level of LPO, and of the defense system, indicated by changes in the levels of SOD and CAT, might result in the development of tissue damage induced by oxygen-derived free radicals.