Inflammation induced by systemic injection of endotoxin can be a good model for endogenous uveitis since ocular inflammation is induced without manipulating the eye. We carried out morphological and biochemical studies in Lewis rats to evaluate the breakdown of the blood-ocular barrier following injection of endotoxin (1 mg/rat) in footpads. Vasodilation was observed as early as 3 hours and became maximum at 18-24 hours after the injection. Unlike in the eye, no inflammatory changes were observed in other organs. Protein and cell contents in the aqueous humor increased significantly as early as 3 hours after the injection and reached a peak level at 24 hours. The protein content returned to the normal level in the following several days, while cells in the aqueous humor remained at a high level even 1 week after the injection. The time-course of the pupillary size was very similar to that of the protein concentration. Furthermore, we examined leukotrienes (LTs) levels in aqueous humor by high-pressure liquid chromatography. LTD4 was detected in the aqueous humor at 6 hours and reached its peak level at 24 hours. The present data indicates that the systemic injection of endotoxin causes the disruption of the blood-ocular barrier soon after the injection and inflammation becomes maximum in 18-24 hours. This model can be used for studying endogenous uveitis and the disruption of the blood-ocular barrier without direct trauma to the eye.