The lymphatic system is an important component of human health and is critical in maintaining microcirculatory flow and immune system homeostasis. During septic shock, increased capillary permeability results in excess filtration of intravascular fluid and solutes producing interstitial edema with subsequent hydrostatic and oncotic gradient breakdown. The accumulation of interstitial fluid results in impaired solute exchange, leukocyte signaling, and aberrancy in capillary flow. Modulation of lymphatic flow during times of interstitial volume overload such as septic shock may decrease interstitial volume resulting in improved perfusion, decreased end-organ damage, and contribute to disease resolution. Multiple studies in both humans and animals have shown nitric oxide to be a potent modulator of lymphatic function. The present study suggests a hypothetical adjunct therapy for patients with septic shock through the use of phosphodiesterase inhibitors, which may improve microcirculatory flow by decreasing interstitial fluid volume via increased lymphatic fluid drainage.Copyright © 2020 The Author. Published by Elsevier Ltd.. All rights reserved.