We investigated the effects of a caerulein-induced acute pancreatitis (AP) on uterus and possible uterine protective effects of melatonin administration. Twenty-eight animals were divided into four groups: (1) control group (n = 7); (2) melatonin group (n = 7); (3) caerulein group (n = 7); (4) melatonin + caerulein group (n = 7). AP was induced by 4 intraperitoneal injection of caerulein given hourly (50 mu g/kg) into young female animals. Melatonin (20 mg/kg) was given via intraperitoneal injection 30 min prior to the induction of AP. The rats were sacrificed by decapitation 12 h after the last injection of caerulein and their uterus were taken for histopathological evaluation. Mean body weight and uterine wet weight was recorded. The H-Score method was used to score the degree of histological changes of endo-myometrium edema, hemorrhage, necrosis, leucocyte infiltration, endometrial proliferation and endometrial thickness. There was no significant difference in the mean body weight observed after treatment in each group. The uterine wet weight differences between the control and caerulein given rats were significant (P < 0.01). The endometrial thickness, edema, hemorrhage, necrosis and leucocyte infiltration of the caerulein group was significantly higher than the control and melatonin groups (P < 0.01). It was observed that preteratment with melatonin normalized histological abnormalities and significantly reduced uterine wet weight as compared with the caerulein only group. Melatonin application may play an important role in the prophylaxis of uterine endometrium arising from adverse effects of caerulein.