The aim of this study was to explore the effects of parenteral supplementation with omega-3 fish oil emulsion (Omegaven) on systemic inflammatory response syndrome (SIRS) during the initial stage of severe acute pancreatitis (SAP). In a prospective, randomized and controlled trial, 60 patients with SAP were randomized either to treat with conventional therapy (Con group, n=30) or conventional therapy plus intravenous supplementation with omega-3 fish oil emulsion 0.2 g/kg every day (FO group, n=30). The effects were analyzed by the SIRS-related indexes. The results showed that APACHE-II scores in FO group were significantly lower, and the gap increased much farther after the 4th day than those in Con group (P<0.05). Fluid equilibrium time became shorter markedly in FO group than in Con group (5.1+/-2.2 days vs 8.4+/-2.3 days). In FO group, SIRS scores were markedly decreased and the SIRS state vanished after the 4th day; Plasma level of TNF-alpha was significantly reduced, while IL-10 decreased markedly, most prominently between the 4th and 7th day, and the ratio of IL-10/TNF-alpha raised as compared with Con group (P<0.05). During the initial stage of SAP, parenteral supplementation with omega-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS, markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines, improve severe condition of illness and may provide a new way to regulate the SIRS.