Abstract Background The roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats. Methods EIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined. Results Treatment with FSE significantly inhibited LPS-induced increases in IL-1β and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN. Conclusion These results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens.