Overweight or obesity in post-menopausal women is known to induce metabolic disorders associated with neuroinflammation. α-lipoic acid (α-LA), which has been clinically used to treat diabetic peripheral neuropathy, has been found to exert anti-inflammatory and neuroprotective effects in patients with Alzheimer's disease (AD). In this study, to investigate the effects of α-LA on neuroinflammatory factors and the levels of hippocampal brain-derived neurotrophic factor (BDNF) in ovariectomized rats fed a high-fat diet (HFD), Wistar ovariectomized rats were fed HFD alone or HFD and treated with α-LA for 12 weeks. Metabolic parameters in serum were detected, real-time polymerase chain reaction (RT-PCR), western blot analysis and ELISA were used to evaluate the levels of inflammatory factors and BDNF in the hippocampus. α-LA markedly reduced body weight, the levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as the levels of leptin and insulin resistance in ovariectomized rats fed HFD. It also significantly increased the levels of serum adiponectin and high-density lipoprotein cholesterol (HDL-C). In the hippocampal tissues of ovariectomized rats fed HFD, the protein and mRNA expression of BDNF was upregulated following the administration of α-LA. Conversely, the levels of interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) were decreased following treatment with α-LA. These findings demonstrate that α-LA significantly increases the expression of BDNF in the hippocampus of obese ovariectomized rats fed HFD, possibly by improving lipid metabolism, enhancing insulin sensitivity and reversing central inflammation.