Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality. We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1. Treatment protocols were saline for group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for group 6, HBO + MER for group 7, and MER for group 8. All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected. Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2). The most favorable results were obtained in HBO treatment groups, especially in HBO + MER group (group 7). Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score. We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease.