<i>Introduction:</i> The liver is critical in multiple processes, including the clearance of endogenous compounds, the synthesis of macromolecules, and organ-specific biotransformation processes. Therefore, the liver’s regenerating capacity is of vital importance. Multiple pathways are activated in the complex process that leads to hepatic regeneration. In the present study, we aimed to evaluate the effect of proton pump inhibitors omeprozole, lansoprazole, and pantoprazole on hepatic regeneration following partial hepatectomy. <i>Materials and Methods:</i> Four groups were formed with 32 rats in each. Partial liver resections were performed for all animals. Omeprazole (71.4 µg/day), lansoprazole (107 µg/day), pantoprazole (143 µg/day) and placebo (0.5 cm³) were administered to the groups respectively. A quarter of the rats in each group were sacrificed on the 1st postoperative day. The rest were sacrificed on the 3rd, 5th and 7th postoperative days. The remnant regenerating liver mass was removed and weighed, and Ki-67 monoclonal antibody levels were measured. <i>Results:</i> There was no statistical difference between the four groups on the first day in evaluating the weight of the liver mass (p = 0.09) and Ki-67 (p = 0.268) levels. Only the omeprazole group showed a difference; the Ki-67 level was lower in the omeprazole group on the 3rd (p = 0.003, p = 0.0001, p = 0.003), 5th (p = 0.017, p = 0.001, p = 0.0001) and 7th (p = 0.0001) days compared to the other groups. Also the weight of the remnant liver mass was lower in the omeprazole group on the 3rd, 5th and 7th (p = 0.0001) days. <i>Conclusion:</i> We figured out that lansoprazole and pantoprazole have no effects on liver regeneration, whereas omeprazole showed a negative effect on hepatic regeneration.