Systemic lupus erythematosus-related acute pancreatitis (SLEAP) has a poor prognosis with a high mortality. We described the clinical features of SLEAP, and discussed the feasibility of plasma exchange (PE) combined with glucocorticosteroids (GC) in short-term prognosis and possible mechanism in reducing serum inflammatory cytokine IL-6 and removing serum lipids. A retrospective study was performed by an independent rheumatologist. Medical records of SLEAP from March 2010 to December 2014 were retrieved from Tongji Hospital information system, and patients were divided into two groups according to whether PE therapy was adopted. Sixteen patients treated with PE in combination with GC were classified as group A, and the other 10 patients who were treated with merely GC were classified as group B. Patients' clinical remission rate and average daily GC dosage after two-week therapy were compared between the two groups. Patients' serum inflammatory cytokines and lipid concentration were compared between baseline and after two-week treatment in both groups. Pearson correlation test was performed to determine association between serum cytokines and Ranson score. SLEDAI score in group A patients at baseline (14.8 +/- 3.1) showed no statistical difference from that in group B (14.1 +/- 3.3). At baseline serum IL-6 levels had no significant difference between group A [13.14 (11.12, 16.57) mg/L] and group B [14.63 (11.37, 16.37) mg/L]; after two-week therapy IL-6 decreased significantly in group A [9.16 (7.93, 10.75)mg/L] while it did not show decreasing trend in group B [13.62 (9.29,17.63) mg/L]. Serum lipid concentration after two-week therapy in group A [(TC=5.02 +/- 0.53, TG=1.46 +/- 0.44) mmol/L] decreased significantly compared to baseline [(TC=6.11 +/- 0.50, TG=2.14 +/- 1.03) mmol/L], while similar tendency was not observed in group B. The remission rate after two-week therapy was higher in group A (70.0%) than in group B (25.0%). Acute pancreatitis (AP) was one of the clinical manifestations of active SLE. PE combined with GC could reduce serum IL-6 level, and remove serum lipid to improve short-term prognosis. Therefore, it might be a safe and effective way in treating SLEAP and was worth continuing to explore its feasibility.