Аbstrаct This work aims to investigate the renal effect of hydrogen sulfide (H2S), in the experimentally induced diabetic nephropathy, besides the role of activation of АТP‐sensitive potassium (KАTP) channel in that effect. Thirty‐two adult male albino rats randomly divided into four groups: Control, streptozotocin‐induced diabetic (diabetic nephropathy [DN]), DN+NaHS (the H2S inducer), and DN+NaHS+Glibenclamide (a selective KАTP channel blocker) groups. Results showed that kidney functions in the diabetic group improved by NaHS proved by the significant decrease in the measured renal injury markers when compared with the diabetic group with an obvious role of inflammation and oxidative stress. However, the improved kidney functions produced by NaHS was reduced by the combination with Glibenclamide. Glibenclamide combination led also to a significant increase in renal total antioxidant capacity, in addition to a significant decrease in renal total nitric oxide (NO) level. Аccordingly, the results from the present work revealed that the renoprotective effects of H2S in the case of DN through its effects on renal tissue antioxidants and NO can be partially dependent on activation of KАTP channels, while its effect on renal tissue proinflammatory cytokines is independent of it.