Background: Severe sepsis increases pro-inflammatory cytokines, causing systemic translocation to the commensal bacteria. A study in Southeast Asia involving 13 public hospitals in 3 countries, including Indonesia, found that sepsis mortality in children was 2% and a 28% incidence of severe sepsis. Low plasma zinc levels were found in severe and critically septic patients in children and adults. Objective: This study aims to explain the mechanism of sepsis improvement after zinc administration through MDA and MMP8 during LPS-induced sepsis in rodents. Material and Methods: We divided samples of 40 rats into four groups of Control, LPS, LPS-Zinc, and Zinc. Blood sampling in 2-hour after LPS or placebo administration to measure zinc level. Zinc was administered in LPS-Zinc and Zinc group and placebo in two other groups. Blood sampling in 8, 24, and 72 hours to measure MDA and MMP-8 by sandwich-ELISA method. Statistical analysis was carried out with one-way ANOVA, Kruskal Wallis, Mann-Whitney, Paired t-tests, Wilcoxon Signed Rank Test, and path analysis. Results: There were decreased in MDA, and MMP-8 serum levels in the LPS-Zinc group compared to the LPS group. Conclusion: Administration of zinc in sepsis improves the condition of sepsis by decreasing pro-inflammatory cytokine and increasing anti-inflammatory cytokine