Many times, diabetes and common/respiratory infection are co-morbid disease conditions. Diabetic patients are more pronefor to developing respiratory infections/pneumonia. The expression and levels of CYP450 and drug transporters are known to modulate in diabetic conditions. Azithromycin and cefixime are widely prescribed medicines for respiratory infections. Therefore,the present study was planned to investigate the effect of diabetes on the pharmacokinetics of azithromycin and cefixime using healthy and dibeticrat as animal model. Azithromycin and cefixime were administered by oral administration to healthy (n=4/group) and diabetic rats (n=4/group). Blood samples were collected from all the animals at predetermined time points. All plasma samples were analyzed by using fit-for-purpose LC-MS/MS method developed for quantification of azithromycin and cefixime in rat plasma. Azithromycin plasma exposure in healthy and diabetic rats were comparable whereas for cefixime diabetic rats showed lower plasma exposure compared to healthy rats. The lower plasma exposure of cefixime in diabetic rats could be due to increased clearance in diabetic rats. The data suggests that azithromycin can be used at the same dose in diabetic patients with that of non-diabetic patients whereas, clinicians need to monitor the therapeutic effect of cefixime in diabetic patients and titre the dose if required.