Klebsiella pneumoniae is both an opportunistic pathogen and a commensal organism. We have previously reported that K. pneumoniae strain IA565 (KpIA565) is nonpathogenic in a murine model of acute pneumonia. In this study, KpIA565 was inoculated into wild-type mice and found to stably colonize and persist in the nasal cavity and gastrointestinal tract of mice for up to 3 weeks postinoculation. Intranasal inoculation of wild-type or germ-free mice with KpIA565 resulted in similar bacterial levels in the nasal cavity, suggesting KpIA565 nasal colonization is independent of normal nasal microbiota. In contrast, KpIA565 gastrointestinal tract colonization was significantly higher in germ-free mice than in wild-type mice, indicating that members of the endogenous microbiota regulate KpIA565 colonization. In the presence of non-specific dextran sodium sulfate-induced inflammation, KpIA565 gastrointestinal tract colonization was significantly higher when compared to non-DSS treated mice. Interestingly, KpIA565 colonization was unaffected by Citrobacter rodentium-induced gastrointestinal tract inflammation. However, gastrointestinal tract colonization with K. pneumoniae strain IA565 had no impact on the inflammatory histopathology in either colitis model. This study is the first to identify and describe mechanisms influencing the growth and behavior of a murine commensal strain of K. pneumoniae.