Acute kidney injury is a frequent and serious complication in patients with severe sepsis. Alpha‐lipoic acid (ALA), a naturally occurring dithiol compound, has been shown to possess anti‐inflammatory and anti‐oxidative properties. In the present study, we investigated whether ALA can attenuate acute kidney injury and improve survival in a rat model of sepsis. Rats were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. ALA (200 mg/kg) was administrated by oral gavage immediately (early treatment) or 12 h (delayed treatment) after the surgical procedure. The results showed that both early and delayed treatment with ALA effectively prolonged survival, improved pathological damages in kidney tissues, and reduced serum blood urea nitrogen (BUN) and creatinine (Cr) levels in CLP‐induced septic rats. Furthermore, early treatment with ALA dramatically inhibited the release of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐1β in serum and reduced the mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and high mobility group box‐1 (HMGB‐1) in kidney tissues from CLP‐induced rats. Finally, CLP‐induced nuclear factor (NF)‐κB activation in kidney tissues was also significantly suppressed by early treatment with ALA. Taken together, we conclude that ALA is able to reduce mortality and attenuate acute kidney injury associated with sepsis, possibly by the anti‐inflammatory actions. ALA may be a promising novel agent for the treatment of conditions associated with septic shock. This article is protected by copyright. All rights reserved.