Active, transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet Slc26a3 (DRA) protein is a candidate mediator of oxalate uptake. To test this hypothesis we evaluated the role of DRA in intestinal oxalate (Ox^2-) and chloride (Cl^-) transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild type (WT) and DRA knockout (DRA KO) mice. In WT mice all segments studied exhibited net Ox^2- and Cl^- absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion which was consistently, and solely, due to a significant reduction in the absorptive unidirectional components. In KO mice, daily urinary oxalate excretion was reduced 66% compared to WT, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and chloride absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscores the importance of transcellular intestinal oxalate absorption in general, and more specifically the DRA exchanger, to oxalate homeostasis.