The increase in lipid peroxidation (LP) is an indirect marker of free radical activation. The products of LP (malonyldialdehyde: MDA) are increased in diabetic patient, particularly those with angiopathy. In this study, the in vitro effect and the mechanism of action captopril, an angiotensin converting enzyme (ACE) inhibitor, on lipid peroxidation in diabetics is investigated. For this purpose, MDA and glutathione levels are studied in erythrocytes of 9 type II diabetics (NIDDM) (mean age: 57 ± 10 yrs, duration of diabetes: 12 ± 6 yrs) and 10 healthy subjects (mean age: 30 ± 5 yrs). The level of lipid peroxides was expressed as MDA release (MDA%). MDA in erythrocytes of type II diabetics has been decreased by the effect of increasing concentrations of captobril (before: 19.47 ± 2.80, after captopril: (2 x 10-5M) 14.21 ± 3.20 MDA%; (4 x 10-5 M) 12.14 ± 3.29 MDA%; (6 x 10-5M) 11.35 ± 2.72 MDA%; (10 x 10-5M) 10.57 ± 2.09 MDA%). In control group, there is a little decrease in LP after preincubation with captopril from 2 to 6 x 10-5M captopril (p > 0.05), but 10 x 10-5M concentration reduced the lipid peroxidation (p < 0.01). However, after preincubated with captopril, glutathione level did not change significantly in the diabetic and normal erythrocytes. In our study, the high levels of lipid peroxidation in erythrocytes from diabetic patients was decreased with preincubation with captopril. Decreasing in the level of lipid peroxidation in vitro was independent on the glutathione level. The reason of this decreasing of the lipid peroxidation may suggest that crosslink binding between MDA and captopril. As result, captopril may also normalize high levels of lipid peroxidation by a mechanism which is not related to its free radical scavenging capacity in vitro.