Hydrogen sulfide (H2S) has been shown to have a potential protective role in a number of disease states including diabetes and various kidney disorders; however, the mechanisms involved are still unclear. The aim of this study was to investigate if H2S effects the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) in human kidney cells. Human mesangial cells and human podocytes were cultured at normal physiological glucose concentration (5.5 mM) and then treated with different H2S donors for a 24-h period. Protein was then extracted from the cells, and the expression levels of HO-1 determined by Western blotting. There was a significant increase in HO-1 expression after treatment with the H2S donors in both mesangial and podocyte cells. These results suggest that H2S has a role in the regulation of HO-1 expression, and the ability to upregulate this antioxidant enzyme maybe a potential mechanism by which H2S exerts its protective effects.