PURPOSE Pycnogenol was used (a) to study its antioxidant activity, (b) to study its effects on lens integrity in organ culture and (c) in vivo to determine whether it could reduce the damage in model diabetic cataract. METHODS For (a) our luminescent antioxidant assay was used, (b) lenses were incubated in medium 199, with 55.6 mM glucose. Lenses were stained with 0.014 mM rhodamine 123 for 15 min to stain mitochondria, immobilized in 1% agarose in M199, and the equatorial region examined by a Zeiss confocal microscope. For (c) cataract grades of streptozotocin diabetic rats fed 1% pycnogenol were followed for 12 weeks. RESULTS (a) Pycnogenol in vitro was an antioxidant when challenged with peroxide. (b) In vitro, when [570 mg/L] pycnogenol in dimethyl sulfoxide (DMSO) was used, lenses turned opaque after 3 d of incubation, in both pycnogenol controls and glucose + pycnogenol. Normal controls (DMSO, n = 4) and controls (n = 4) remained clear after 8 d of incubation. After 3 d of incubation with pycnogenol, cumulative protein leakage was greater than 0.28 mg/mL versus 8 d controls (0.018 mg/mL). Similar damage occurred at pycnogenol concentrations as low as 20 mg/L. The 20 mg/L pycnogenol control showed mitochondrial death, and calcium concentration in the lens equatorial differentiating fiber cells increased. (c) In vivo feeding pycnogenol resulted in similar growth and body condition for diabetic rats, and lower cataract grades at 9 and 11 weeks: final serum glucose levels were not significantly different, but glycohemoglobin A1 levels were significantly lower (83.9% of normal, p < 0.05) in pycnogenol-fed diabetic rats. CONCLUSIONS Although it appears that pycnogenol has a potential toxic effect on incubated lenses, it appears in vivo to have a marginal protective effect, and also significantly reduces glycation of proteins. Supported by Cognis US (formerly Henkel Chemical Co.) and Horphag Research.