OBJECTIVE - To investigate whether intraperitoneal insulin infusion (IPII) decreases the levels of circulating chylomicron remnants in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS - Eight nonobese, normolipidemic IDDM patients were studied twice: before (while on subcutaneous insulin) and 6 months after initiation of IPII by a programmable implanted medication system. Fasting and mean blood glucose, HbA1, and lipid values were determined. Blood samples were also drawn before and every 2 h for 10 h after ingestion of a fat meal (corn oil + Vitamin A). Triglycerides (TGs), apolipoprotein B (apoB), and retinyl esters were determined over time in two TG-rich lipoprotein subfractions (S(f) > 100 and S(f) 20-100) isolated from plasma by density-gradient ultracentrifugation. RESULTS - IPII slightly decreased the mean blood glucose from 7.8 ± 1.1 to 7.4 ± 1.1 mmol/l (mean ± SD, P = 0.027, paired Student's t test) and the HbA1 from 9.4 ± 1.5 to 8.7 ± 1.2 (NS). TG and apoB levels in postprandial S(f) > 100 and S(f) 20-100 were not changed by IPII. On IPII, however, retinyl ester levels in S(f) > 100 decreased (P = 0.05, analysis of variance [ANOVA]) and tended to be lower in S(f)20-100 (P = 0.075). In addition, following IPII, the retinyl ester:apoB ratio was lower in S(f) > 100 (P = 0.0002) and marginally lower (P = 0.06) in S(f) 20-100. CONCLUSIONS - IPII decreased chylomicron remnant levels, which might decrease the atherosclerotic risk in IDDM. Since glycemic control was only slightly improved, the effect was most likely due to the intraperitoneal route of delivery.