Abstract: Objective: To investigate the effects of recombinant human beta-defensin-3 (rhBD3) on acute inflammation induced by Porphyromanas gingivilis lipopolysaccharide (P.g-LPS) in apolipoprotein E knockout (ApoE-/-) mice and murine RAW264.7 macrophages. Methods: Male ApoE-/- mice (20 weeks old) were randomly divided into PBS control group, P.g-LPS group and P.g-LPS+rhBD3 group, and were stimulated by intraperitoneal injection. Serum inflammation markers (MCP-1, TNF-α, IL-6, IL-1β and NO) secretion levels were measured 2 hours later. The effects of rhBD3 on inflammation induced by P.g-LPS in RAW264.7 cells were also evaluated by detecting the secretion levels and mRNA relative expression levels of inflammation markers in culture supernatant and cells, respectively. Results: Serum MCP-1, TNF-α, IL-6 and NO secretion levels in P.g-LPS group of ApoE-/- mice were significantly upregulated, while the levels of MCP-1, TNF-α and NO decreased significantly in P.g-LPS+rhBD3 group. The increased levels of TNF-α and NO in culture supernatant and mRNA relative expression levels of TNF-α and IL-6 in RWA264.7 cells stimulated by P.g-LPS could be downregulated by rhBD3. Conclusion: rhBD3 has suppressive effect on acute inflammation induced by P.g-LPS in vivo and in vitro. It may play a modulating role in the interaction between periodontitis and hyperlipidemia.