Objective: To investigate the effect of warm saline peritoneal lavage on acute necrotizing pancreatitis (ANP) in rats and its mechanism. Methods: Seventy-five SD rats were equally randomized into sham operation group, ANP model group (model group), and warm saline peritoneal lavage pretreatment plus ANP model group (pretreatment group). Rats were sacrificed at 6 h after surgery, and then serum concentration of amylase and cytokines were measured, the HSP70 and p38MAPK mRNA expressions in the pancreatic tissues were determined by RT-PCR, and the NF-κB expression in the pancreatic tissues was examined by immunohistochemical staining, respectively. Results: Compared with sham operation group, the serum levels of amylase, TNF-α, IL-6, and IL-8 were markedly increased in both model group and pretreatment group, but the increasing degrees of all the above parameters in pretreatment group were less than those in model group; the HSP70 and p38MAPK mRNA expressions in both model group and pretreatment group were remarkably increased, but the HSP70 mRNA expression level was higher while the p38MAPK mRNA expression level was lower in pretreatment group than that in model group, and all the above differences had statistical significance (all P<0.05). The pancreatic NF-κB showed weak-positive expression in sham operation group, strong-positive expression in model group, and moderate-positive expression in pretreatment group. Conclusion: Warm saline peritoneal lavage can improve the pathophysiological process of ANP, and the mechanism may be attributed to its inducing HSP70 expression which may inhibit the p38MAPK and NF-κB activities and reduce the expression of inflammatory cytokines.