The present study was undertaken to identify whether the age at induction of experimental diabetes modifies macrophage infiltration in the kidney. Renal macrophage infiltration was studied 10 days after the induction of experimental diabetes in 4-week-old pre-pubertal and 12-week-old adult male rats of normotensive [Wistar-Kyoto (WKY) rats] and hypertensive (spontaneously hypertensive rats, SHRs) background. Renal macrophage infiltration was evaluated by immunohistochemistry for ED1. Plasma glucose levels were similar in all diabetic groups. Adult SHRs were hypertensive, and induction of diabetes did not alter blood pressure (BP) in any group. Induction of diabetes in pre-pubertal rats did not induce macrophage infiltration in the kidney. However, in adult rats, tubulointerstitial macrophage infiltration was increased in both WKY (22.86 +/- 3.93 vs 7.86 +/- 2.16 per high-power field, P < 0.001) and SHR (26.41 +/- 5.91 vs 11.48 +/- 1.23, P < 0.001) groups after induction of diabetes. Glomerular macrophage infiltration was also increased after induction of diabetes in the adult WKY group (1.83 +/- 0.50 vs 1.16 +/- 0.26 per glomerular cross section, P=0.029), which was not significant in the adult SHRs (2.52 +/- 0.34 vs 1.95 +/- 0.35). We conclude that the pre-pubertal induction of diabetes apparently protects against early renal macrophage infiltration, while the induction of diabetes in adults induces exaggerated macrophage infiltration in the kidney.22710451049