Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (Mphi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium chain triglyceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-gamma addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on Mphi surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 0.5%: 100) FO decreased the expression of HLA-DR when added alone [in simultaneously-activated Mphi, for 0.1%: 70 (59+/-73); for 0.25%: 51 (48+/-56); and for 0.5%: 52.5 (50+/-58)] or in association with MCTSO [in simultaneously-activated Mphi, for 0.1%: 50.5 (47+/-61); for 25%: 49 (45+/-52); and for 0.5%: 51 (44+/-54) and in previously-activated Mphi, for 1.0%: 63 (44+/-88); for 0.25%: 70 (41+/-88); and for 0.5%: 59.5 (39+/-79)] in culture medium (Friedman p<0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated Mphi [for 0.1%: 87.5 (75+/-93); for 0.25%: 111 (98+/-118); and for 0.5%: 101.5 (84+/-113)]. Results show that parenteral FO modulates the expression of HLA-DR on human Mphi surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.