Introduction: Understanding the molecular mechanism of cells is key to developing novel treatments. In our initial effort, survival and replication of intracellular Salmonella enterica serovar Typhimurium (S. Typhimurium) in vitamin A & D supplemented human macrophage THP-1 cell line was evaluated over a week to develop a molecular correlates with acute and chronic infection. In addition the infected macrophages were treated with Peptide Nucleic Acid (PNA) to kill intracellular Salmonella by determining actual colony-forming units (CFUs) from cell lysates using Trypticase Soy Agar (TSA) plates. Materials and Methods: Adding 10mM retinoic acid and 26mM vitamin D3 (RAVD) activated The THP-1 cells grown in RPMI 1640 medium containing 10% fetal bovine serum (FBS) and 1% of Penicillin-Streptomycin (P/S). After three days of activation the THP-1 cells were infected with S. Typhimurium at a 1:10 multiplicity of infection (MOI). Then the THP-1 cells were lysed using 0.5% sodium dioxycholate on day 0, 1 and 7 to determine intracellular and extracellular CFUs. In another set such infected cells were treated overnight with 100, and 50 uM concentrations of PNAs specifically designed against the aceA, aceB, gcvP, dnaK and control scrambled genes of S. Typhimurium. Extracellular and intracellular CFUs were calculated by serial dilutions of supernatants and lysates plated on TSA plates. The plates were incubated at 37°C for 24 hours. Microsoft excel 2007 was used for the data analysis and to determine significant differences by student " T " test. Results: In all the groups treated with PNA, extracellular S. Typhimurium was higher, and statistically different between day O and 1 (P <0.02), as well between day 0 and 7 (P<0.01). Where as intracellular S. Typhimurium was higher at day 0 before PNA treatment, but with significant loss in the group treated with the lowest concentration of PNA at day 1 (P<0.001), and day 7 (P value <0.001) compared to day 0. Conclusion: The RAVD activated infected THP-1 cells not only survived, but also could support the growth and survival of S. Typhimurium for 7 days suggesting the infected cells could be used to study both the acute as well as chronic infection. In addition the groups treated with dnaK PNA showed the most significant loss of intracellular Salmonella compared to day 0. Then the CFUs in all cases remained relatively same as at day 1 levels without much variability until day 7, suggesting that the intracellular S. Typhimurium may have become latent. Messenger RNA analysis for latency-associated genes using specific primers are under way.