Puromycin aminonucleoside (PA) nephrosis is associated with a significant increase in the glomerular macrophage number during peak proteinuria. The significance of this observation remains uncertain. An essential fatty acid-deficient (EFAD) diet depletes normal rat glomeruli of resident macrophages and alters glomerular eicosanoid metabolism. In this study, we found that an EFAD diet, administered only for the duration of the acute nephrotic phase, significantly ameliorated the recurrent albuminuria, renal dysfunction, and morphological injury characteristic of the late, recurrent phase of chronic aminonucleoside nephrosis. Glomerular macrophage number, isolated glomerular thromboxane B2 production, and circulating leukocyte and monocyte counts were significantly reduced in nephrotic rats on the EFAD diet 2 wk after PA injection, which temporally corresponds to peak albuminuria. The exact mechanism(s) by which the EFAD diet conferred protection in the late phase of chronic aminonucleoside nephrosis and lowered glomerular macrophage number during the acute nephrotic phase remain to be elucidated.