Objective: Macrophages are involved in obesity-associated inflammation and severe acute pancreatitis (SAP) development. However, the role of adipose tissue macrophages (ATMs) in obesity-related SAP has not been fully elucidated. We investigated the relationship between ATMs and inflammatory responses in SAP model mice fed a high-fat diet (HFD). Methods: SAP was induced in animal models via intraperitoneal injections of caerulein and lipopolysaccharide (LPS). SAP severity was evaluated, both morphologically and biochemically, and macrophage infiltration in the pancreas and epididymal adipose tissue was measured. We also analyzed apoptosis levels, polarization of the ATMs, and expression of inflammatory mediators in epididymal adipose tissue. Results: Obesity increased disease severity in SAP animals. Increased macrophage infiltration in the pancreas induced by SAP was found in both normal diet (ND)- and HFD-fed mice. Total ATM infiltration in epididymal adipose tissue was elevated by HFD, while a significant decrease in infiltration was observed in both the ND + SAP and HFD + SAP groups. The apoptosis levels of ATMs were reduced in the HFD group, but were markedly enhanced in both the ND + SAP and HFD + SAP groups compared to their respective control groups. Higher levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were observed in the HFD + SAP than in the ND + SAP group. Increased proportion of M1 type ATMs was induced by both HFD and SAP. Conclusions: Total ATM infiltration was decreased in epididymal adipose tissue of SAP animals. ATM polarization to the M1 type resulted in an amplified inflammatory response in obese mice with SAP.Keywords: Adipose tissue macrophages; Apoptosis; Inflammation; Obesity; Severe acute pancreatitis.