Objective: To monitor the alterations of TNF-α, IL-1β and IL-6 levels in patients with severe acute pancreatitis (SAP), so as to determine the influence and significance of enteral nutrition (EN) on excessive activation of leucocytes during the early course of SAP. Methods: Seventy-nine SAP patients were divided into EN group and parenteral nutrition (PN) group, and all the patients received the basic treatment according to guidelines for SAP management. In PN group (25 cases), the PN support was initiated on the third day after onset and continued until oral intake was resumed. In the EN group (54 cases), the EN support was started at different time periods after onset (the first, fourth or sixth day after onset) and continued until oral intake was resumed. The drop extent in TNF-α, IL-1β and IL-6 levels of the two groups were compared. Results: The TNF-α, IL-1β and IL-6 levels in both groups decreased gradually after treatment. However, from the fifth day after treatment, the drop extents of above parameters in each EN group were significantly evident than those of PN group (P<0.05), and the earlier the EN support was initiated, the more evident did the above parameters decrease (P<0.05). Conclusion: Early EN support can effectively reduce the TNF-α, IL-1β and IL-6 levels in SAP patients, and it is faster than PN support in reducing the duration of excessive activation of leucocytes during SAP, which is beneficial to the recovery of the patients.