The NLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1β and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is activated in the urinary tract by a variety of infectious and non-infectious insults. In this study, we investigated the role of the NLRP3 inflammasome by comparing the pathophysiology of methicillin-resistant (MRSA) ascending UTI in wild-type (WT) and mice. The difference in the bacterial burden detected in the urinary tracts of MRSA-infected WT and was not statistically significant at 6, 24, and 72 h post-infection (hpi). The levels of pro-inflammatory cytokines and chemokines as well as the numbers of granulocytes recruited to bladder and kidney tissues at 24 hpi were also similar between and WT mice. The histopathological analysis of MRSA-infected bladder and kidney sections from and WT mice showed similar inflammation. Overall, these results suggest that MRSA-induced urinary NLRP3 activity does not play a role in the pathophysiology of the ascending UTI.