Purpose: To investigate whether a protein kinase C (PKC) inhibitor and melatonin prevent proliferative vitreoretinopathy (PVR). Methods: Twenty pigmented rabbits were used in this study. All rabbits except controls received an intravitreal injection of 0.15 ml (75,000 units) of platelet-rich plasma into their left eye. The animals were divided into four groups: group I was treated with intravitreal injection of 0.15 ml (100 mu mol/ ml) of PKC inhibitor ( chelerythrine chloride), group II received 1 ml (4 mg/kg) of intraperitoneal melatonin for 3 days, group III received nothing (blank group), and group IV (control group) received only 0.5 ml of 1% ethanol intraperitoneally for 3 days. Proliferative changes were graded in a masked fashion by indirect ophthalmoscopy for a 15-day follow-up period. The malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite levels were measured in the itreous humor. Results: The grades of PVR were A and B in group I and II, treated with PKC inhibitor and melatonin, respectively. The PVR grade in the blank group was C-D. The mean MDA level in group I (4.2 +/- 0.9 mu mol/ l) was significantly lower than in the blank group (6.0 +/- 1.0 mu mol/ l; p < 0.05). The mean GSH level in group I (66.3 +/- 8.8 mu mol/ l) was not significantly different from that in the blank group (p > 0.05). The MDA and GSH levels in group II were 3.2 +/- 0.7 and 70.1 +/- 13.3 mu mol/ l, respectively. Both these levels were significantly different from those of the blank group (p < 0.05). The NO levels in both treatment groups were significantly lower than in the blank group (p < 0.001). Conclusion: These findings suggest an inhibitory effect of PKC inhibitor and melatonin on PVR. The inhibition of PVR development was associated with lower MDA and NO levels with higher GSH levels in the treatment groups. Copyright (c) 2006 S. Karger AG, Basel.