To study the effect of an oral prostaglandin E1 (PGE1) derivative and/or lipo PGE1 on the onset of diabetes, these agents were administered to Bio-Breeding/Worcester/Tokyo (BB/W/Tky) rats from 4 to 13 weeks of age. Lymphocyte subsets in peripheral blood from normal Wistar and BB/W/Tky rats were measured before and for one week after administration of PGE1 using laser flow cytometry. Results showed that 14/16 (87.5%) of the BB/W/Tky rats administered PGE1 developed diabetes vs. 6/12 (50%) in the control BB/W/Tky rats. In normal Wistar rats, PGE1 significantly increased the W3/25+OX39+ and OX8+OX39+ cells. In BB/W/Tky rats, PGE1 significantly increased the OX19+OX6+, OX19+OX39+, W3/25+OX6+, W3/25+OX39+, OX8+, OX8+OX6+, OX8+OX39+ and OX39+ cells, while decreasing the OX6+ cells. We conclude that the administration of PGE1 to BB/W/Tky rats accelerates the development of spontaneous diabetes and alters the surface markers of lymphocytes.