The signaling lipid sphingosine 1-phosphate (S1P), which is abundant in lymph, guides T cell exit from lymph nodes (LN) into lymph by signaling through T cell S1P receptor 1 (S1PR1). By trapping pathogenic T cells within LN and preventing them from reaching their target tissues, drugs targeting S1PR1 have been successful in treating autoimmune diseases such as multiple sclerosis, and are being tested in dermatomyositis, psoriasis, graft versus host disease, and subacute cutaneous lupus erythematosus. Simultaneous inhibition of S1PR1 within the cardiovascular system, however, results in adverse effects on the heart and vasculature. At steady state, the major facilitator superfamily transporter SPNS2 is required to supply lymph S1P, which drives lymphocyte egress, but does not play a major role in maintaining the levels of blood S1P required for cardiovascular function. Inhibition of SPNS2 was therefore proposed as a strategy to trap autoreactive T cells in LN while avoiding cardiovascular side effects. However, it was unknown whether SPNS2 remained necessary to supply lymph S1P during an immune response, or whether other compensatory transporters were up-regulated during inflammation. Here, using an OT-II TCR transgenic CD4 T cell model of dermal inflammation, we demonstrate that in SPNS2-deficient mice, there is a 10-fold decrease in T cell accumulation in inflamed skin compared with littermate controls. This is not due to differential T cell proliferation, as draining LN contain similar numbers of OT-II cells. Consistent with a LN egress defect, there is a decrease in activated OT-II cells in the lymph and blood of SPNS2-deficient mice compared to controls. We then developed a method to measure S1P gradients within lymphatics of inflamed LN and demonstrated that SPNS2 supplies the lymph S1P that guides T cells out of LN with an ongoing immune response. This work adds to our understanding of lymphocyte trafficking in inflammation and suggests a new, more targeted way to treat inflammatory diseases.