Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin (LPS, 1 mg/kg, ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS Vc/C1 units had reduced responses to histamine, nicotine and CO2 gas applied to the ocular surface, whereas unit responses were increased 7d after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7d after LPS. Units at the Vi/Vc transition also had reduced responses to histamine- and CO2 2d after LPS but no enhancement was seen at 7d. Tear volume evoked by CO2 was reduced 2d after LPS and returned toward control values by 7d, while CO2-evoked eye blinks were normal at 2d and increased 7d after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.