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Despite the role of monocytes in the pathogenesis of severe acute pancreatitis (SAP), it remains unclear how different subtypes of monocytes regulate and contribute to this pathogenesis.We examined the numbers of different subsets of monocytes by flow cytometry in 21 SAP, 15 mild acute pancreatitis (MAP) and 13 healthy controls (HC). The concentrations of plasma cytokines were assessed by cytometric bead array. Disease severity was evaluated based on the acute physiology and chronic health evaluation (APACHE) II score and plasma C-reactive proteins (CRP) levels.Compared with the numbers in MAP patients and HC, we observed that the numbers of CD14+CD163−, CD14+CD163−MAC387+, CD14+CD163−IL-12+ M1 monocytes, and CD115+, CD204+, IL-10+ M2 monocytes were significantly increased in SAP patients. In addition, these patients showed higher plasma levels of interleukin (IL)-12 and IL-10. Furthermore, the number of CD14+CD163−, CD14+CD163−MAC387+ M1 monocytes and the plasma IL-12 concentration showed a positive association with the CRP level, while the number of CD204+, IL-10+ M2 monocytes and the plasma IL-10 concentration showed a positive correlation with the APACHE II score. Importantly, the CD115+ M2 subset displayed a positive correlation with both the CRP level and APACHE II score, and treatment of SAP significantly reduced the number of this subset.The CD14+CD163+CD115+ M2 monocyte count appears to be important factor in determining the severity and prognosis of SAP. Both the pro- and anti-inflammatory monocytes appear to participate in the pathogenesis of SAP.The CD14+CD163+CD115+ monocytes may be important factor in determining the severity of SAP.Both M1 and M2 monocytes participate in the pathogenesis of SAP.Treatment alleviated the inflammation and reduced the numbers of different subsets of monocytes.