Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and interventions leading to their reduction are associated with improvement of the hypertension. The present studies examined the evolution of the interstitial inflammation in the natural course of the SHR to gain insight on the potential role of interstitial immune cell accumulation in the development of hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3wk group, n = 11 and WKY-3wk group, n = 10), 11 weeks (SHR-11wk group, n = 5 and WKY-11wk group, n = 5) and 24 weeks (SHR-24wk group, n = 10 and WKY-24wk group, n = 10). The SHR-3wk group was normotensive and older SHR developed hypertension that was severe in the SHR-24wk group. Tubulointerstitial accumulation of lymphocytes, macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding subunit of NF-ĸB and activation of NF-ĸB in the kidney were all significantly increased (p < 0.01) in the prehypertensive SHR-3wk group and augmented progressively, with the highest values in the SHR-24wk group. The SHR-24wk group showed increased (p < 0.001) helper (CD4) T cell infiltration and a high CD4/CD8 ratio. These findings are consistent with the possibility that activation of NF-ĸB and renal interstitial infiltration of immune cells may be part of the pathophysiologic process that drives hypertension in the SHR.