Objectives: Podocyte loss is well known to play a critical role in the early progression of diabetic nephropathy. A growing number of studies are paying attention to necroptosis, a programmed form of cell necrosis, as a mechanism of podocyte loss. Although necroptosis is a recently established concept, the significance of receptor interacting serine/threonine kinase 3 (RIPK3), a gene that encodes for the homonymous enzyme RIPK3 responsible for the progression of necroptosis, is well-studied. Also, effects of curcumin on high glucose-induced podocyte necroptosis have not been reported yet. Therefore, this study investigated RIPK3 expression in high glucose-treated podocytes to identify the involvement of necroptosis via RIPK3 pathway and the effects of curcumin treatment on RIPK3-dependent podocytopathy in a hyperglycemic environment. Methods: Differentiated mouse podocytes were challenged with either normal (5.6 mM) or high (30 mM) glucose medium for 24 hours. Drugs(10μM GSK'872. 50μM NAC, and 50μM Curcumin) were treated simultaneously with HG for 24 hours. Intracellular ROS generation was analyzed using 2’-7’ dichlorofluorescein diacetate (CM-H2DCF-DA). To measure superoxide anion, one of the ROS types, superoxide anion assay kit was used. To determine the effect of curcumin on high glucose-induced podocyte damage, we performed an immunofluorescence assay, quantitative real time-PCR, and western blot. Results: Decreased nephrin and increaed CCL2, TGF-β and VEGF proteins in HG-stimulated podocytes were restored by curcumin. HG-induced ROS generation and upregulated RIPK3 were also restored by curcumin. To check the association of RIPK3 and ROS, HG-treated podocytes were stimulated with RIPK3 inhibitor GSK'872 and NAC. we confirmed that RIPK3 inhibitor decreased RIPK3 expression as well as ROS generation. Conclusions: Renoprotective effects of curcumin might be associated with its ability to inhibit high glucose-induced RIPK3 expression by inhibiting oxidative stress. Curcumin might be a potential therapeutic agent to minimize the progression of podocytopathy caused by diabetes as an inhibitor of RIPK3.