In the present study, we examined the long-term effect of oxidative stress induced neurodegeneration on sterol concentrations in striatum and serum of Wistar and Lewis rats. Three weeks after treatment with 3-nitropropionic acid, no differences in 24S-hydroxycholesterol concentrations were observed in striatal homogenates and serum. Ratios of striatal campesterol to cholesterol were higher after 3-nitropropionic acid treatment as compared to controls of both rat strains suggesting an increased passage of this exogenous plant sterol across the blood-brain-barrier. Ratios of lathosterol to cholesterol in serum and striatum were lower in treated rats as compared with controls of both rat strains. Absolute concentrations of serum and striatal cholesterol precursors and plant sterols differed between the controls of both rat strains. It was concluded that the changes observed in sterol concentrations in the striatum and serum indicate that cholesterol homeostasis may be affected during neurodegenerative processes associated with blood-brain-barrier damage.