Non-pathogenic trypanosomes of the subgenus Herpetosoma are normally host specific, and laboratory models include Trypanosoma lewisi in rats and Trypanosoma musculi in mice. Two isolates of Trypanosoma grosi, originating from Apodemus agrarius and Apodemus peninsulae, grew well in Mongolian jirds, Meriones unguiculatus, after intraperitoneal inoculation of 2×105 or a minimum 500 bloodstream forms. The course of T. grosi infection in jirds resembled T. musculi infection in mice, rather than T. lewisi infection in rats. At week 2 to 3 p.i. trypanosomes disappeared from the bloodstream, and neither prednisolone treatment nor splenectomy prevented parasite elimination from the bloodstream. However, these treatments induced a marked increase in peak parasite counts. Regardless of prednisolone treatment or splenectomy, all jirds after day 21 p.i. became resistant to the reinfection. Although no trypanosomes were detected in the bloodstream of recovered jirds, dividing parasites persisted in the medullary capillaries of the kidney, like T. musculi infection in mice. We propose the T. grosi infection in jirds as an additional laboratory model for the study of non-pathogenic trypanosomes.