Introduction: Ciprofloxacin and meropenem have effects on intestinal bacteria that are responsible for pancreatic infection, and on the basis of recent data it has been argued that probiotics, especially those used in the food industry, could improve efforts to prevent and treat secondary pancreatic infections by inhibiting bacterial translocation. Aims: To evaluate the effects of probiotic treatment alone or in combination with early administration of two different antibiotics on serum amylase, pancreatic histopathology, bacterial translocation, and oxidative markers. Methodology: Acute pancreatitis was induced in rats with 3% sodium taurocholate (1 mL/kg intraductally), except in group VI (sham group). After the stabilization period, the rats were divided into seven groups (n = 20) randomly. At hour 6 after injection, group 1 rats received probiotic Saccharomyces boulardii (25 mg/d orally q.d.), group II received meropenem (60 mg/kg intraperitoneally b.i.d.), group III received ciprofloxacin (40 mg/kg intraperitoneally b.i.d.), group IV received the same dose of probiotic plus meropenem, and group V received probiotic plus ciprofloxacin. Treatment was not given to group VI (sham group) and group VII (pancreatitis group). At hour 48 after induction, specimens were collected. Results and Conclusion: Although histopathologic scores in treatment groups were found to be lower than in group VII, the difference was statistically significant only in group V (p < 0.001). In evaluation of oxidative stress, we found that MDA levels decreased and SOD levels increased in treatment groups in comparison with levels in group VII. Probiotic treatment alone reduced bacterial translocation. Probiotic-antibiotic combination therapy was shown to improve histopathologic scores and oxidative parameters.