α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I—control (0.9% NaCl i.v.); II—α-LA (60 mg/kg b.w. i.v.); III—LPS (30 mg/kg b.w. i.v.); and IV—LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (−SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase −SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.Graphical Abstract