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Nanoparticles (NPs) promise to address current limitations for treating acute pancreatitis (AP)viainflammatory cell-mediated sequestration. However, very few studies have explored the influence of NP size on their behavior in different stages of AP. The present work investigated the biodistribution of IR780 loaded mesoporous silica nanoparticles (MSNs) with sizes of 60, 150 or 300 nm after intravenous administration to rats of mild AP (MAP) or severe AP (SAP). Four hours after administration, MSN150was present to a much greater extent in the pancreas than MSN60or MSN300, irrespective of disease severity. MSN150was present to a lower extent in pancreas, intestine and ascites in SAP than MAP rats, indicating weaker passive targeting in SAP rats. This may reflect greater blood loss and slower blood flow in SAP. These findings may guide the rational engineering of NPs with respect to particle size and disease severity for AP therapy.