Diabetic nephropathy is a major cause of end-stage renal failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with beneficial effects in pathology of many conditions. However, its role in diabetic nephropathy is unclear. This study examined the protective role of H2S producing enzyme cystathionine gamma lyase (CSE) in kidney impairment induced by diabetes. Diabetes was induced in male Wistar rats by high fat diet for 12 weeks followed by a single i.p. injection of streptozotocin (35mg/kg). Animals were divided into: control (chow fed), diabetic non-treated group (DM), diabetic + L-cysteine (50 mg/kg/day, i.p.) and diabetic + PAG (37.5 mg/kg/day, i.p.) for 4 weeks. 
Diabetes decreased CSE expression and activity, increased H2O2 and MDA in kidney tissue with impaired SOD and CAT activity. L-cysteine treatment improved kidney function (serum urea and creatinine levels), decreased MDA, H2O2 production and increased renal SOD and CAT activity. L-CYS attenuated diabetes-induced expression of NF-κB. Administration of PAG deteriorated the kidney function with significant increase in oxidative stress and inflammation status. 
L-CYS rescued kidney dysfunction by reducing oxidative stress, NF-κB expression and decreasing the apoptotic enzyme caspase-3. Recovery of CSE expression mRNA and its activity may also contribute to the beneficial effects of L-CYS.