Purpose: Titanium (Ti) is frequently used in dental implants because of its excellent corrosion resistance, mechanical properties, and biocompatibility. However, Ti ions may be slowly released as a result of corrosion, contributing to peri-implantitis, a major cause of dental implant failure. This study examined the influence of Ti ions on cytokine levels in murine splenocytes, an immunocompetent cell type, stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) and the influence of Ti ions on splenocyte viability. Materials and Methods: Splenocytes were prepared from 5- to 10-week-old male C57BL/6 mice and BALB/c mice. Cytokine levels in culture supernatants from murine splenocytes stimulated with A actinomycetemcomitans LPS were determined with enzyme-linked immunosorbent assay. A tetrazolium salt assay was carried out to evaluate the cytotoxicity of Ti ions against murine splenocytes. Results: The present study demonstrated that Ti ions influence cytokine levels in LPS-stimulated splenocytes. Significantly higher values (P .05) were observed for interleukins 1β, 6, and 10; interferon-γ; tumor necrosis factor alpha; and granulocyte macrophage colony-stimulating factor in the culture supernatants of LPS-stimulated splenocytes of both mouse strains in the presence of Ti ions, as compared to the absence of Ti ions. Tetrazolium salt assay confirmed that the Ti ions used in this study did not affect the viability of murine splenocytes. Conclusion: This study suggests that Ti ions enhanced cytokine production induced by periodontopathic bacterial LPS. Keywords: cytokine, lipopolysaccharide, murine splenocyte, titanium ion