This Turkish laboratory animal-based study looked at the effects of alpha-lipoic acid on inflammation, oxidative status, and tissue integrity in an animal model of experimentally induced acute rhinosinusitis and to compare these effects with antibiotic treatment using cephalosporins. Alpha-lipoic acid is an antioxidant agent with potential anti-inflammatory properties and is produced from octanoic acid. A total of 30 healthy Wistar Albino rats were randomly divided into six groups, with five rats in each group. In the control group, staphylococcus aureus (SA) was not induced in the rats, whilst in another group SA was induced but not treatment applied. Over a 10-day period, the remaining SA-induced groups were treated daily either with 50 mg/kg cefazolin (SA + cefazolin), alpha-lipoic acid 100 mg/kg (SA + ALA 100), alpha-lipoic acid 200 mg/kg (SA + ALA 200), or ALA 200 mg/kg+cefazolin 50 mg/kg (SA + ALA 200 + cefazolin). At the end of the test, the maxillary sinus mucosa was removed and histological analysis was performed, as well as analysis for superoxide dismutase activity and glutathione, malondialdehyde, tumour necrosis factor-alpha mRNA, and interleukin-1β mRNA levels - all markers of oxidative stress. Histopathological examination showed less inflammatory changes in the SA + cefazolin groups and in the ALA groups compared to the control group. In terms of molecular results there were increased levels of malondialdehyde, tumour necrosis factor-alpha mRNA, and interleukin-1β mRNA, in the SA-induced group compared to the healthy group (p<0.05) and the levels in the SA + ALA 200 + cefazolin group were similar to that of the healthy group (p<0.05). In terms of biochemical markers of inflammation, there were increased levels of superoxide dismutase activity and glutathione level in the SA group compared to the healthy group. All the treated groups had levels of inflammatory markers close to that of the healthy group, but this was most significant with the SA + ALA 200 + cefazolin group. This study suggests that using a potent antioxidant, such as ALA, along with antibiotic treatment can be more effective in reducing oxidative stress and cytokine levels in the management of bacterial rhinosinusitis.