Previous reports showed that many cognitive deficits arise in patients exhibiting symptoms of urinary tract infections (UTI) including neuropsychiatric disorders. In our laboratory, we have shown that E-coli induced UTI in adult rats caused a significant decrease in neurogenesis and impaired cognitive and memory skills. No studies have explored the mechanism of action and the effect of chronic inflammation mimicking UTI on neurogenesis and brain plasticity. Here, we aim to investigate the effect of chronic peripheral inflammation via lipopolysaccharide (LPS) instillation in the urothelium on cognitive functions, memory, and hippocampal neurogenesis. In this project, adult male Sprague-Dawley rats received four transurethral instillations of LPS over a period of 4 days to mimic chronic UTI-like associated inflammation. Control groups were instilled with sterile saline. Bromodeoxyuridine (BrdU) analog was injected 24 hours before euthanasia to assess hippocampal neural stem cells (NSCs) proliferation. To assess neurogenesis, BrdU was injected 3 weeks before euthanasia. In addition, a battery of behavioral tests including heat sensitivity, open field, Y-maze, and Object Recognition (NOR) tests were used to assess thermal pain, spontaneous/exploratory motor behavior, cognitive ability and working memory, respectively. This study demonstrated that chronic inflammation induced by repetitive instillations of LPS in the urinary bladder was associated with decreased hippocampal neurogenesis and impairment of cognitive-like behavior in rats. As such, this will provide experimental evidence about the association of UTI and cognitive disorders reported in clinical observations.