Aim To investigate the possible therapeutic effects of alpha-lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro-CT parameters. Methodology The study was approved by the Animal Ethics Committee of the Near East University. Thirty-two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4-weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg(-1), for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg(-1), for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro-CT. Groups of data were compared with a two-way analysis of variance (two-way anova) followed by Sidak's multiple comparison tests. Values of P TNF-alpha, IL-1 beta, MMP-1, MMP-2 levels were significantly lower in AP + ALA group compared with AP group (P < 0.05). There was a significant difference between the AP and AP + ALA groups according to assessment of the inflammatory scores (P < 0.05). The periapical inflammatory infiltrates were significantly more severe (P < 0.05) in the AP group. The AP + ALA group exhibited lower values both in terms of surface area and volume of resorption cavities than the AP group and this difference was significant (P < 0.05). Conclusion alpha-lipoic acid treatment provided therapeutic effects on the inhibition of periapical bone loss.