Diabetic nephropathy is the major cause of mortality or morbidity in type 2 diabetes patients. Podocyte is known to play a significant role in the progression of diabetic nephropathy and previous studies have shown an elevated oxidative stress level in high glucose-induced podocyte injury. Curcumin, a hydrophobic polyphenol responsible for the yellow color in Curcuma longa, has gathered attention from various research fields with its natural anti-oxidative, anti-inflammatory, and anti-apoptotic effects. Nonetheless, the effect of curcumin on high glucose-induced podocyte injury is not well known. Thus, this study investigated the effect of curcumin on high glucose-induced podocyte injury caused by oxidative stress or inflammatory response.  Podocytes were incubated with normal glucose (5.5 mM) and high glucose (30 mM) in the presence or absence of curcumin (50 uM) for 24 hrs. Intracellular reactive oxygen species (ROS) generation was analyzed using 2’-7’ dichlorofluorescein diacetate (CM-H2DCF-DA). Western blot and quantitative real time-PCR, and immunofluorescence analysis were carried out to evaluate the effects of curcumin on high glucose-induced podocyte injury. CCL2 (C-C motif chemokine ligand 2) level in high glucose-treated podocytes was measured by ELISA. Increased ROS in podocytes stimulated by protein was also reduced with curcumin. Furthermore, curcumin treatment has significantly restored the upregulation of VEGF, TGF-β, and CCL2 and downregulation of nephrin at mRNA levels in cultured podocytes exposed to high glucose environment. In addition, high glucose-induced changes in the expression of TGF-β, nephrin, and CCL2 at protein levels were considerably reverted to the original level with curcumin treatment. High glucose-mediated F-actin rearrangement of podocytes was recovered significantly by curcumin treatment. The research suggests that curcumin may have a novel therapeutic effect on high glucose-induced podocyte injury by regulating RI high glucose was improved with curcumin treatment. High glucose-induced increase of RIPK3 PK3, oxidative stress, and inflammatory pathway.