Background <p>Laparoscopy, while minimally invasive, leads to local and systemic inflammatory responses due to pneumoperitoneum. Recent studies highlight the anti-inflammatory effects of magnesium and its deficiency’s link to inflammation. This study aimed to investigate the dose-dependent local and systemic anti-inflammatory effects of Mg²⁺ on PP-related perioperative inflammatory response in an animal model.</p> Methods <p>Thirty-six rats were divided into four groups: MG250, MG500, pneumoperitoneum group (PG), and control group (CG). PG, MG250, and MG500 underwent pneumoperitoneum for 60&#xa0;min at 12 mmHg. MG250 and MG500 received 250&#xa0;mg/kg and 500&#xa0;mg/kg of i.p. MgSO4 respectively, while PG received 0.9% saline. No additional procedures were performed on CG. Serum and peritoneal tissue samples were collected from all groups. Tissue samples were examined for inflammatory cell infiltration, congestion, and cellularoedema. Systemic inflammation was evaluated by measuring TNF-α, IL-1, IL-10, and MPO levels in serum samples.</p> Results <p>Comparisons between CG and PG revealed that pneumoperitoneum amplified the local inflammatory response. Regarding systemic markers, only MPO levels were higher in PG compared to CG (<i>p</i> &lt; 0.001). In MG250, both histopathological findings and MPO levels showed a lower inflammatory response compared to PG. No significant differences were observed between MG500 and PG.</p> Conclusions <p>The application of i.p. MgSO4 during the perioperative period may exhibit anti-inflammatory effects at an appropriate dose. However, further large-scale, prospective, and randomized studies are necessary to better understand the local and systemic effects of Mg²⁺ doses.</p> Clinical trial number <p>Not applicable.</p>