RATIONALE: LPS-dependent activation of endothelial cells can increase the level of inflammatory mediators leading to angiopathy. Serum antiendotoxin (anti-LPS) antibodies may neutralize the biologic activity of LPS. METHODS: 56 patients (104 eyes) with diabetic retinopathy (DR) were assessed and divided into 5 groups: (1) 20 patients (40 eyes) with DR, characterized by non-uniformity of venous size and sclerosis of the arteries; (2) 12 patients (24 eyes) with nonproliferative DR; (3) 8 patients (16 eyes) with preproliferative DR; (4) 8 patients (16 eyes) with proliferative DR; and (5) 7 patients (10 eyes) with proliferative DR complicated by neovascular glaucoma. The control group had 97 healthy persons. Levels of serum anti-LPS-IgA, anti-LPS-IgM and anti-LPS-IgG were determined by ELISA. RESULTS: The highest levels of anti-LPS-IgA and anti-LPS-IgG were in groups 2 and 3, especially in group 2, anti-LPS-IgA 2.5 to 5.5 times other groups (p<0.01) and anti-LPS-IgG 2.4 to 6.0 times other groups (p<0.01). Anti-LPS-IgA in group 3 was 4.4 to 9.7 times greater (p<0.01) than groups 1 and 5, and anti-LPS-IgG 2.3 to 5.9 times greater (p<0.01). Levels of anti-LPS-IgA in group 5 were 2.2 to 9.7 fold less (p<0.01), and anti-LPS-IgG 2.5 to 6.0 fold less (p<0.01) than in other groups, and levels of anti-LPS-IgA and anti-LPS-IgG 3.9 and 5.5 fold less (p<0.01) than controls. Groups 1-5 all had levels of anti-LPS-IgM 1.2 to 2.7 fold less (p<0.01) than controls. CONCLUSIONS: Antiendotoxin antibodies were greatest in patients with nonproliferative retinopathy and less in proliferative retinopathy, suggesting a role for antiendotoxin response in pathologic retinopathy development.