Objective To investigate the effect of hyperlipidemia (HL) on the pancreatic injuries during acute necrotizing pancreatitis (ANP) as well as the activation of nuclear factor kappa B ( NF-κB) and pancreatic acinar cell apoptosis. Methods Fifty SD male rats were randomly divided into control group, hyperlipidemia ( HL) group, ANP group and HL + ANP group. Rats in control group were fed with balanced diet for 2 weeks, and underwent opening and closing of the abdomen. Rats in HL group received fat emulsion lavage, and then underwent opening and closing of the abdomen. Rats in ANP group were fed with balanced diet for 2 weeks, and were induced by retrograde injection of sodium taurocholate into the bili-pancreatic duct to establish the ANP model. Rats in HL + ANP group received fat emulsion lavage for 2 weeks, and were induced by retrograde injection of sodium taurocholate into the bili-pancreatic duct to establish the ANP model. NF-κB p65 and Fas, FasL protein expression were determined by immunohistochemical method and the apoptosis in pancreatic acinar cell were detected by TUNEL. Results Two weeks after fat emulsion lavage, rats in HL and HL + ANP group had significantly higher serum level of lipid. Lipid vacuoles were present in some pancreatic cells in the rats of HL group, and middle number of inflammatory cells infiltration was found, the activation of NF-κB was slightly enhanced; and the expression of Fas, FasL was also enhanced. Apoptosis index increased from (0.62 ±0.28)% to (3.3S ±1.12)%. Massive pancreatic tissue necrosis, large amount of inflammatory cells infiltration was found in ANP group. NF-κB p65 was present in large number of pancreatic nucleus. The expression of Fas and FasL was also increased; the apoptosis index was (2.20±1.78)%. The degree of pancreatic necrosis was greater in HL + ANP group than that in ANP group (3.4 ± 0.7 vs. 2.4 ± 1.1, P <0.05). The positive rate and density of NF-κB expression was higher than that in ANP group; and the expression of Fas and FasL was decreased more than that in ANP group; the apoptosis index was (0.93 ± 0.87)% , which was significantly lower than that in ANP group (P <0.05). Conclusions High level of lipid can increase the activation of NF-κB and inhibit the acinar cell apoptosis, and decrease the expression of Fas and FasL, increase the pancreatic tissue necrosis, therefore in order to attenuate the injury of pancreas, it is essential to control blood lipid.