The high prevalence of dry eye syndrome, often associated with systemic inflammatory response (SIR) and oxidative/ nitrosative stress, underscores the need to develop effective cytoprotective agents targeting the lacrimal glands. Sulfo- raphane, a naturally occurring compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising therapeutic candidate. This study evaluated the effects of sulforaphane on oxidative/nitrosative stress parameters in the lacrimal glands of rats subjected to lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The experiment was conducted on adult male Wistar rats, randomly assigned to three groups: 1st group was control; 2nd group included rats modeled with SIR induced by intraperitoneal administration of Salmonella typhi LPS; the 3rd group, rats received sulforaphane (10 mg/kg, intragastrically) daily during the final week of LPS- induced SIR induction. The following markers were assessed in lacrimal gland homogenates: superoxide anion radical ( • O 2 - ) production, activities of constitutive and inducible nitric oxide synthase (cNOS and iNOS), ornithine decarboxylase activity, peroxynitrite levels, S-nitrosothiols, and aquaporin-5 concentration. Sulforaphane administration resulted in a significant reduction • O 2 - production by 28.6% in microsomes, 32.4% in mitochondria, and 50.7% in NADPH oxidase of leukocytes. Inducible NOS activity decreased by 36.4%, while cNOS and ornithine decarboxylase activities increased by 89.3% and 58.9%, respectively; the cNOS coupling index rose by 157%; peroxynitrite and S-nitrosothiol concentrations decreased by 60.1% and 13.7%, respectively. Aquaporin-5 levels were nearly restored to normal, 0.51 ± 0.01 pg/ml vs. 0.27 ± 0.01 pg/ml in the 2nd group. These findings confirm the cytoprotective efficacy of sulforaphane on the lacrimal glands under LPS-induced SIR.