Renal protection of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) in diabetic mice against inflammatory injury was examined. Each agent at 0.5 and 1 g/L was added to the drinking water for 10 weeks. SAC or SPC intake significantly reduced plasma blood urea nitrogen level and increased creatinine clearance (P<0.05). These treatments significantly lowered renal level of reactive oxygen species, nitric oxide, interleukin-6, tumor necrosis factor-alpha and prostaglandin E2 in diabetic mice (P<0.05). Renal mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, protein kinase C (PKC)-alpha, PKC-beta and PKC-gamma was enhanced in diabetic mice (P<0.05); however, SAC or SPC treatments dose-dependently declined mRNA expression of these factors (P<0.05). Nuclear factor kappa B (NF-κB) activity, mRNA expression and protein production in kidney of diabetic mice were significantly increased (P<0.05). SAC or SPC intake dose-dependently suppressed NF-κB activity, NF-κB p65 mRNA expression and protein level (P<0.05). Diabetes also enhanced renal protein expression of mitogen-activated protein kinase (P<0.05). SAC and SPC, only at high dose, significantly suppressed protein production of p-p38 and p-ERK1/2 (P<0.05). Renal mRNA expression and protein generation of peroxisome proliferator activated receptor (PPAR)-alpha and PPAR-gamma were significantly down-regulated in diabetic mice (P<0.05), but the intake of SAC or SPC at high dose up-regulated PPAR-alpha and PPAR-gamma (P<0.05). These findings support that SAC and SPC are potent anti-inflammatory agents against diabetic kidney diseases.