The therapeutic effects of hydrogen-rich saline (HRS) have been reported for a wide range of diseases mainly via selectively reducing the amount of reactive oxygen species. Oxidative stress plays an important role in the pathogenesis of uveitis and endotoxin-induced uveitis (EIU). In this study, we investigated whether HRS can mitigate EIU in rats. Sprague-Dawley rats were randomly divided into Norm group, Model group, HRS group, dexamethasone (DEX) group, and rats in the latter three groups were injected with equal amount of lipopolysaccharide (LPS) to induce EIU of different severities (by 1 mg/kg of LPS, or 1/8 mg/kg of LPS). Rats in HRS group were injected with HRS intraperitoneally at three different modes to purse an ameliorating effect of EIU (10 mL/kg of HRS immediately after injection of 1 mg/kg of LPS, 20 mL/kg of HRS once a day for 1 week before injection of 1 mg/kg of LPS and at 0, 0.5, 1, 2, 6, 8, 12 hours after LPS administration, or 20 mL/kg of HRS once a day for 1 week before injection of 1/8 mg/kg of LPS, and at 0, 0.5, 1, 2, 6, 8, 12, 24 hours and once a day for 3 weeks after LPS administration). Rats of DEX group were injected with 1 mL/kg of DEX solution intraperitoneally immediately after LPS administration. Rats in Norm and Model groups did not receive any treatment. All rats were examined under slit lamp microscope and graded according to the clinical signs of uveitis. Electroretinogram, quantitative analysis of protein in aqueous humor (AqH) and histological examination of iris and ciliary body were also carried out. Our results showed that HRS did not obviously ameliorate the signs of uveitis under slit lamp examination and the inflammatory cells infiltration around iris and cilliary body of EIU induced by 1 mg/kg or 1/8 mg/kg of LPS (P > 0.05), while DEX significantly reduced the inflammation reflected by the above two indicators (P < 0.05). The impaired retinal function of mild EIU induced by 1/8 mg/kg of LPS, showed by delay of peak time of b-wave of Dark adapted 3.0 electroretinogram, was not significantly restored by HRS (P > 0.05), while DEX had an obvious therapeutic effect (P < 0.05). However, HRS exerted an inhibition trend on elevation of protein in AqH of EIU induced by 1 mg/kg of LPS, and significantly reduced the increasing amount of protein in AqH of mild EIU induced by 1/8 mg/kg of LPS (P < 0.05). In conclusion, HRS could not obviously mitigate EIU in rats, while it could inhibit the elevation of AqH protein.