Background: Apigenin (AP) is a flavonoid substance, in nature abundance, which is described to have anti-inflammatory and anti-oxidative effects. We investigated the effect of AP on acute pancreatitis (ACP) by measuring the values of interleukin-6 (IL-6), interleukin-18 (IL-18) and resistin (R) in serum and CD45 as well as high mobility group box 1 protein (HMGB1) in intestinal tissue using a rat experimental model. Methods: 126male Wistar rats, (age 90-120 days, body weight 250-350 g), were used. The rats were divided in three groups: Sham (S), Control (C) and Apigenin (Ap). The S group comprised 20 rats, which underwent laparotomy and closure of the abdominal wall. The C group comprised 56 rats, which underwent ligation of the pancreatic duct to induce ACP. The Ap group comprised 50 rats, which, after induction of ACP, received AP. Each group was divided into 5 subgroups according to the time euthanasia was performed (i.e., 6, 12, 24, 48 and 72 hours after laparotomy). Blood and intestinal tissue were collected. Results: Comparing the C with the Ap group we observed an improvement in IL-6 and IL-18 examined in serum and in HMGB1 as well as in CD45 expression in intestinal mucosa. Following AP administration IL-6 and IL-18 decreased at 12h in the Ap group. HMGB1 increased significantly in C group and decreased remarkably in Ap group over time. CD45 decreased at 24h after AP administration in the Ap group. In contrast to the previous results R remained at low levels in the Ap group.I Conclusions: AP administration in rats in a bilio-pancreatic duct ligation experimental model of ACP appears to have a protective effect on intestine and serum parameters reducing the severity of ACP. Therefore administration of that substance in humans could improve the damage of the organs affected in the early stages of ACP.