Ovine toxoplasmosis is an important reproductive disease in sheep, and is also a zoonosis, where tissue cysts are a major source of infection for humans. Vaccination to reduce the number of tissue cysts in food animals has been suggested as a possible approach to protect public health. To enable effective development of these strategies, it is important to understand the host-parasite interactions at those locations where tissue cysts are formed and within animal species of interest, i. e. food animals. In this study, we investigated whether oral infection of lambs with Toxoplasma gondii oocysts may be used as an experimental model in sheep to study this interaction, with the main objective being to detect parasite cysts and host immune reaction within different tissues and organs using histological methods. Lambs were orally infected with 5-103 and 5-105 sporulated T. gondii oocysts and culled at 2, 3, 5 and 6 weeks post infection (WPI). The lambs showed no clinical signs other than fever, and lesions appeared mainly in the brain, characterized by glial foci and perivascular cuffs, and heart, denoted by foci of interstitial myositis. Tissue cysts and tachyzoite-like structures were recognized in the brain, heart, lung and lymph nodes at all the time points studied. This study shows that oral infection with sporoulated oocysts in lambs could provides a model for investigating the host-parasite interaction in situ during the development of tissue cysts.