As a worldwide environmental pollutant, cadmium (Cd) and its compounds (Cd2+)lead to the nephrotoxicity[1].In this study, we aimed to establish a kidney injury model in mice with acute Cd2+ exposure.We administered by successively intraperitoneal injection for seven days with different doses of 0-5 mg/kg CdCl2 in ICR mice.It was found that the ratio of BUN/CRE was decreased in CdCl2 groups.The histological analysis showed that shrinkage of glomerulus and the degeneration of tubules were observed in 1 and 5 mg/kg CdC12 groups compared with control group, which indicated Cd2+ resulted in renal dysfunction.In the kidney, cyclooxygenase-2 (COX-2), endoplasmic reticulum (ER) stress associated proteins, GRP78, p-eIF2 and CHOP, and autophagy marker LC3-Ⅱ protein were sharply increased in Cd2+ groups.Moreover, significantly increase of COX-2, GRP78, LC3-Ⅱ proteins were found in kidney tubules with immunohistochemical analysis in Cd-exposed mice.Our studies presented that pretreatment with celecoxib (50 mg/kg) rescued the autophagy in kidney via inhibition of COX-2.Taken together, the results in vivo indicated that Cd2+ lead to the dysfunction of kidney through the induction of ER stress and autophagy related with the overexpression of COX-2.The present study provides insight that COX-2 may be a potential promising preventive target against Cd2+-induced nephrotoxicity.