In order to further understand the role of the cholinergic anti-inflammatory pathway, the authors determined the effects of burn plasma from donor rats (DRs) on the microvascular circulation of healthy recipient rats and whether these could be altered by pretreatment with physostigmine (PT). DRs underwent thermal injury (100°C water, 12 seconds, 30% BSA) for positive controls. For negative controls DRs underwent sham burn (same procedure but water at 37°C). DR-plasma (harvested 4 hours posttrauma) was transferred to healthy rats. Bolus injection of PT (70 μg/kg body weight) was performed 15 minutes before starting the infusion of DR-plasma in the study group. Intravital microscopy was performed in mesenteric venules (0/60/120 minutes). Edema was assessed by fluorescein isothiocyanate (FITC)-albumin extravasation. Additionally, leukocyte rolling and sticking (cells/mm) as well as hemodynamic parameters were assessed. Burn plasma transfer significantly increases albumin extravasation in healthy individuals when compared with sham-burn treatment. Additional bolus administration of PT (70 μg/kg body weight) to burn plasma treatment reduces plasma extravasation to sham-burn levels. PT also attenuates leukocyte-endothelial interactions. After 120 minutes no significant changes in the systemic circulation (mean arterial pressure, heart rate, wall shear rate) were found between the groups. Burn plasma transfer results in significant increases in plasma extravasation and leukocyte-endothelial wall adherence, which are reversed by pretreatment with PT. These results suggest that the cholinergic anti-inflammatory pathway may play a role in the microcirculatory response to thermal injury.