Although recruited neutrophils function as first-line defense to remove bacteria, delayed apoptosis is implicated in persistent inflammation leading to organ injury. Leukotrien B₄, n-6 polyunsaturated fatty acids (PUFAs) product, is one of the mediators that delay neutrophil apoptosis. The mechanism of the beneficial effects of supplementation of fish oil-based long-chain n-3 PUFAs in parenteral nutrition for critically ill patients has not been fully understood. One possible mechanism is the less inflammatory n-3 PUFAs products can compete with proinflammatory n-6 PUFAs products for access to the enzymes. The aim of this study was to determine whether n-3 PUFA rich parenteral nutrition may alter the composition of fatty acids in the neutrophil membrane and restore delay of neutrophil apoptosis during endotoxin-induced systemic inflammation in rats. The animals in group 1 were treated with 20% Hicaliq NC-N in Neoparen-2 for three days. The animals in group 2 (referred to as n-6 PUFA-rich parenteral nutrition) were given parenteral nutrition solutions containing 20% soybean oil in Neoparen-2 (n-6/n-3 = 10). The animals in group 3 (referred to as n-3 PUFA-rich parenteral nutrition) were administered parenteral nutrition consisting of 10% soybean oil and 10% fish oil emulsion (n-6/n-3 = 1.3). The n-3/n-6 ratio of the neutrophil membrane was significantly increased in group 3 and was associated with restored lipopolysaccharide-delayed-apoptosis of neutrophils in bone marrow cells and increased production of leukotriene B₅ from peritoneal neutrophils stimulated by lipopolysaccharide. Our preliminary results showed that n-3 PUFA-rich parenteral nutrition regulated neutrophil apoptosis and prevented synthesis of pro-inflammatory eicosanoids, explaining the protective effects seen in the clinical setting.