We examined the immunoregulating effect of 22-oxa-1α, 25-dihydroxyvitamin D₃ (22-oxa-1α, 25(OH)₂D₃), a synthetic analogue of vitamin D₃ with an oxygen atom at C₂₂ in the side chain skeleton, on spontaneously developing autoimmune disorders in MRL/Mp-lpr/lpr (MRL/l) mice. The oral administration of the compound significantly prolonged the average life span of the mice and showed a significant reduction in proteinuria. Histopathological investigations also revealed that pathological conditions such as renal arthritis, granuloma or arthritis of the knee joints were much lighter in the treated group than in the untreated group. Furthermore, the lymphocyte phenotypes in thymus, lymphnode, and spleen were partially normalized and became similar to those found in young control animals by the treatment with 22-oxa-1α, 25(OH)₂D₃. These results suggest that this compound inhibits the development of lupus nephritis in MRL/l mice and may be therapeutically effective on the mice.