Urine neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury and indicates tubular damage. Lupus nephritis-associated renal injury is characterized by damage to the glomeruli and tubular portions of the kidneys. Therefore, NGAL concentrations are expected to vary according to the severity of systemic lupus erythematosus (SLE). In this study, samples from (NZB × NZW) F1 mice at an advanced stage of SLE were used to determine whether serum and urine NGAL concentrations or the urine NGAL:creatinine (uNGAL/C) ratio can be used to reflect diet, disease state, and treatment efficacy. Additionally, the relationship between the levels of NGAL and various cytokines in the serum in SLE was evaluated. Mice were divided into the following four groups (n=15): CN, chow diet and no treatment (saline; intraperitonially injected [i.p.]; 200 μL/day); CP, chow diet and methylprednisolone (i.p.; 5 mg/kg/day); HN, high-fat diet and no treatment (saline [i.p.]; 200 μL/day); and HP, high-fat diet and methylprednisolone treatment (i.p.; 5 mg/kg/day) every day from 6 to 42 weeks of age. The serum and urine NGAL levels and uNGAL/C values were significantly lower in the CP group than those in the CN group. Further, serum NGAL concentration demonstrated a strong positive correlation with urine NGAL levels, uNGAL/C, urine protein concentrations, urine protein:creatinine ratio, and the expression of several cytokines associated with SLE pathogenesis (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and interferon-induced protein [IP]-10). These results suggest that NGAL has a strong positive correlation with the clinicopathological parameters and several key cytokines in SLE.