Objectives . In the present study, we investigated the protective effects of Shen-Fu injection (SFI) on a caerulein-induced rat pancreatitis (AP) model. Methods . SFI was given to rats in the SFI treated group through intraperitoneal injection. Blood and pancreas samples were collected for serological and histopathological studies. Results . Our results showed that AP caused significant decrease in tissue glutathione (GSH) and serum IL-4 and IL-10, while pancreatic malondialdehyde (MDA) and myeloperoxidase (MPO) were increased. Furthermore, TNF- α , IL-1 β , amylase, and lipase levels were also significantly increased. On the other hand, SFI treatment reserved all these biochemical indices as well as histopathologic alterations that were induced by caerulein. Conclusion . Our findings suggest that the SFI protects against caerulein-induced AP in rats via modulation of cytokines, oxidative stress, and Nuclear Factor-kappa B (NF- κ B) activity.