This study examined aquaporin 4 (AQP4) and Kir4.1 (a potassium channel subunit) in normal and diabetic adult Sprague-Dawley rats, and determined the effect of minocycline treatment. Retinal expression of the AQP4 and Kir4.1 genes was examined using double immuno fluorescence, Western blot analysis, and real-time reverse transcription-polymerase chain reaction. Retinal levels of vascular endothelial growth factor (VEGF), ionized calcium-binding adaptor molecule (Iba)-1 and interleukin (IL)-1β were also ascertained. The blood-retinal barrier (BRB) and retinal oedema were assessed using rhodamine isothiocyanate. AQP4, VEGF, Iba-1, and IL-1β mRNA and protein levels increased, and Kir4.1 mRNA and protein levels decreased, in diabetic rat retinas. Both BRB disruption and retinal oedema were also observed in these retinas. In diabetic rats, minocycline treatment decreased AQP4, VEGF, Iba-1 and IL-1β levels and retinal oedema, and increased Kir4.1 levels. These findings suggest that minocycline might be beneficial for retinal fluid clearance and reduction of retinal oedema in diabetic retinopathy.