Feline leukemia virus (FeLV) infection was discovered over 50 years ago; however, the serious clinical changes associated with FeLV infection still have great importance in the diagnosis, prevention, and clinical management of symptomatic patients. Progressive infection with FeLV leads to a reduction in the patient's life expectancy and quality of life. This report describes the use of an antiretroviral integrase inhibitor, raltegravir, in two cats with natural FeLV infection. Raltegravir was administered orally at a dose of 40 mg/cat every 12 h in both cases. In case one, 13 weeks after starting raltegravir, RNA loads were undetectable, while proviral DNA loads were still detectable. In case two, proviral DNA loads were undetectable after 32 weeks of medication, while RNA loads were undetectable throughout the treatment. No adverse effects or laboratory test abnormalities were detected with the use of raltegravir in either patient. The patients are currently clinically healthy, still receiving the drug, and are under close observation. To our knowledge, this is the first report describing the use of raltegravir in naturally infected FeLV-positive cats and its effects on circulating viral load. Moreover, the patients described here were followed-up for a longer period than those in previously reported cases.